ENDOCRINE SYSTEM

INTRODUCTION

All the physiological activities of the body are regulated by two major systems
namely the nervous system and the endocrine system. These two systems
interact with one another in regulating body functions. . Endocrine system
functions by secreting chemical substances called hormones or hormone-like
substances (chemical messengers).

Endocrine glands are ductless; that is, they do not have ducts to take their
secretions to specific sites. Instead, hormones are secreted directly into capillaries
and circulate in the blood throughout the body. Each hormone then exerts very
specific effects on certain organs, called target organs or target tissues. Some
hormones, such as insulin and thyroxine, have many target organs. Other
hormones, such as calcitonin and some pituitary gland hormones, have only one
or a few target organs. In general, the endocrine system and its hormones help
regulate growth, the use of foods to produce energy, resistance to stress, the pH
of body fluids and fluid balance, and reproduction.

HORMONES

Hormones are peptides categorized in one of three classes:

• Peptides and proteins,

• Steroids, or
• Amines.

Each class differs in its biosynthetic pathway: Peptide and protein hormones are
synthesized from amino acids; steroid hormones are derivatives of cholesterol;
and amine hormones are derivatives of tyrosine.
Classification of hormones depending upon chemical nature

Steroids Protein Amines

Aldosterone Growth hormone (GH) Thyroxine (T4 )

11-deoxycorticosterone Thyroid-stimulating Triiodothyronine (T3 )

hormone (TSH)
Cortisol Adrenaline (Epinephrine)
Adrenocorticotropic
Corticosterone hormone (ACTH) Noradrenaline
(Norepinephrine)
Testosterone Follicle-stimulating
hormone (FSH) Dopamine
Dihydrotestosterone
Luteinizing hormone (LH)
Dehydroepiandrosterone
Prolactin
Androstenedione
Antidiuretic hormone
Estrogen Progesterone (ADH)

Oxytocin

Parathormone

Calcitonin

Insulin

Glucagon

Somatostatin

Pancreatic polypeptide

Human chorionic
gonadotropin (HCG)
 Human chorionic
somatomammotropin.

The secretion of hormones can be stimulated by:

• Nervous impulses (e.g secretion of catecholamine such as adrenaline and

noradrenaline from the adrenal medulla due to direct stimulation from the
sympathetic nervous system),

• Hormones (e.g secretion of TSH from the anterior pituitary directly

stimulates secretion of T4 from the thyroid gland) or

• Changes in the body levels of ions and nutrients (humoral e.g PTH secreted
in response to low levels of calcium ions in blood ).

Further regulation of hormone release is then often controlled by negative

feedback mechanisms.

Hormone does not act directly on target cells. First it combines with receptor
present on the target cells and forms a hormone-receptor complex. This
hormonereceptor complex induces various changes or reactions in the target
cells.

HORMONE RECEPTORS

Hormone receptors are the large proteins present in the target cells. Each cell has
thousands of receptors. Important characteristic feature of the receptors is that,
each receptor is specific for one single hormone, i.e. each receptor can combine
with only one hormone. Thus, a hormone can act on a target cell, only if the
target cell has the receptor for that particular hormone.

Hormone receptors are situated either in cell membrane (protein hormones and
adrenal medullary hormones) or cytoplasm (steroid hormones) or nucleus
(thyroid hormones) of the target cells.
Excess secretion of a particular hormone leads to a decrease in the number of
receptors specific for that hormone, this is referred to as down regulation while
the reverse leads to up regulation of the receptors specific for that hormone.
(clinical significance)

Hormone in the form of hormone-receptor complex enters the target cell by

means of endocytosis and executes the actions. The whole process is called
internalization after which these receptors are either degraded or recycled. New
recptors are also formed.

MECHANISM OF HORMONE ACTION

The hormone-receptor complex executes its hormonal action by any one of the
following mechanisms:

• By altering permeability of cell membrane

• By activating intracellular enzyme
• By acting on genes.
 ➢ By altering permeability of cell membrane

Neurotransmitters in synapse or neuromuscular junction act by changing the

permeability of postsynaptic membrane e.g acetylcholine

➢ By activating intracellular enzyme

Protein hormones and the catecholamines act by activating the intracellular

enzymes.

First Messenger

The hormone which acts on a target cell, is called first messenger or chemical
mediator. It combines with the receptor and forms hormone-receptor complex.

Second Messenger

Hormone-receptor complex activates the enzymes of the cell and causes the
formation of another substance called the second messenger or intracellular
hormonal mediator. Second messenger produces the effects of the hormone
inside the cells. Protein hormones and the catecholamines act through second
messenger. Most common second messenger is cyclic AMP, others include
calcium & calmodulin, Inositol triphosphate (IP3), Diacylglycerol (DAG), Cyclic
guanosine monophosphate (cGMP) etc

Cyclic AMP

Cyclic AMP, cAMP or cyclic adenosine 3’5’- monophosphate acts as a second

messenger for protein hormones and catecholamines.

Formation of cAMP – Role of G proteins

G proteins or guanosine nucleotide-binding proteins are the membrane proteins

situated on the inner surface of cell membrane. These proteins play an important
role in the formation of cAMP. Each G protein molecule is made up of trimeric
(three) subunits called α, β and γ subunits.
The α subunit can bind either guanosine monophosphate (GDP) or guanosine
diphosphate (GTP), and it has an intrinsic enzyme activity called GTPase activity.
The α-subunit is responsible for most of the biological actions. When GDP is
bound to the α subunit, the G protein is inactive; when GTP is bound, the G
protein is active and can perform its coupling function.

The β and γ subunits always bind together to form the β-γ dimmer. It can also
bring about some actions.

In the inactivated G protein, both α-GDP unit and β-γ dimmer are united.

A breakdown of the events that leads to the formation of cAMP are as follows:

i. Hormone binds with the receptor in the cell membrane and forms the
hormone-receptor complex.
ii. It activates the G protein.
iii. G protein releases GDP from α-GDP.
iv. The α-subunit now binds with a new molecule of GTP, i.e. the GDP is
exchanged for GTP.
v. This exchange triggers the dissociation of α-GTP unit and β-γ dimmer
from the receptor.
vi. Both α-GTP unit and β-γ dimmer now activate the second messenger
pathways. The α-GTP unit activates the enzyme adenyl cyclase, which is
also present in the cell membrane. Most of the adenyl cyclase protrudes
into the cytoplasm of the cell from inner surface of the cell membrane.
vii. Activated adenyl cyclase converts the adenosine triphosphate of the
cytoplasm into cyclic adenosine monophosphate (cAMP). When the
action is over, α-subunit hydrolyzes the attached GTP to GDP by its
GTPase activity. This allows the reunion of α-subunit with β-γ dimmer
and the commencement of a new cycle.

Cyclic AMP executes the actions of hormone inside the cell by stimulating the
enzymes like protein kinase A. These actions include contraction and relaxation of
muscle fibers, alteration in the permeability of cell membrane, synthesis of
substances inside the cell, Secretion or release of substances by target cell, and
other physiological activities of the target cell.

In summary, a cell’s response to a hormone is determined by the enzymes within

the cell, that is, the reactions of which the cell is capable. These reactions are
brought about by the first messenger, the hormone, which stimulates the
formation of the second messenger, cyclic AMP. Cyclic AMP then activates the
cell’s enzymes to elicit a response to the hormone.
 ➢ By acting on genes

Thyroid and steroid hormones execute their function by acting on genes in the
target cells. The sequence of events that occur during the activation of genes are
as follows:

i. Hormone enters the interior of cell and binds with receptor in cytoplasm
(steroid hormone) or in nucleus (thyroid hormone) and forms
hormonereceptor complex.
ii. Hormone-receptor complex moves towards the DNA and binds with
DNA.
iii. This increases transcription of mRNA.
iv. The mRNA moves out of nucleus and reaches ribosomes and activates
them.
v. Activated ribosomes produce large quantities of proteins.
 vi. These proteins produce physiological responses in the target cells.

ENDOCRINE GLANDS

The endocrine glands of the body includes hypothalamus, anterior and posterior
pituitary, thyroid, parathyroid, pancreas, adrenal, kidneys, ovaries, testes, corpus
luteum and placenta.

Diagram showing major endocrine glands

THE HYPOTHALAMUS AS AN ENDOCRINE GLAND

The Hypothalamus is a very important part of the central nervous system present
in the forebrain. It controls the firing of the autonomic nervous system as well as
the functioning of the endocrine system. Thus, it plays a central role in controlling
all the essential processes of life. The hypothalamus is a part of the forebrain. It is
considered to be a part of the diencephalon.

Location: It is located just below the thalamus and forms the floor and the lower
part of the lateral walls of the third ventricle. Anteriorly, it extends up to the optic
chiasma and posteriorly it is continuous with the tegmentum of midbrain.

Structure: It is composed of a cluster of neurons that are arranged into

nuclei. The hypothalamus communicates with the rest of the body
via three routes: Bloodstream or endocrine connections, Nervous connections
and Cerebrospinal fluid.

The hypothalamus uses the bloodstream to communicate with the pituitary

gland. The cells of the pituitary gland release hormones in response to the
regulating factors or hormones released by the hypothalamus. These regulatory
factors reach the pituitary gland via the hypophyseal portal system of veins.
Hypothalamus also uses nervous connections to communicate with the pituitary
gland. These neurons synthesize the oxytocin and vasopressin hormones, which
are stored in the axonal terminals in the posterior pituitary and are released on
demand.

Blood supply: Hypothalamus receives blood mainly from the hypophyseal artery,
a branch of the anterior cerebral artery. All the blood from the hypothalamus is
drained into the hypothalamohypophyseal system of veins and distributed to the
pituitary gland. From the pituitary gland, the blood is drained via the hypophyseal
vein.
Hormones/Secretions of the hypothalamus: It secretes two important
hormones; vasopressin and oxytocin though these hormones are released from
the posterior pituitary. They are produced by the neurons in the hypothalamus
and are stored in the axonal endings present in the posterior pituitary.

It also produces releasing factors or inhibitory factors called neurohormones for

controlling the hormones released by the pituitary gland (precisely the anterior
pituitary gland). These factors include:

1. Growth hormone-releasing hormone (GHRH)

2. Growth hormone-releasing polypeptide (GHRP)
3. Growth hormone inhibiting hormone also called somatostatin (GHIH)
4. Prolactin releasing hormone (PRH)
5. Prolactin inhibiting hormone (PIH)
6. Corticotropin-releasing hormone (CRH)
7. Thyrotropin-releasing hormone (TRH)
8. Luteinizing hormone-releasing
hormone or gonadotropin releasing hormone (LHRH or GnRH)
THE PITUITARY GLAND

Pituitary gland or hypophysis is a small endocrine gland with a diameter of 1 cm

and weight of 0.5 to 1 g.

Location: It is situated in a depression called ‘sella turcica’, present in the

sphenoid bone at the base of skull.

Structure: It is connected with the hypothalamus by the pituitary stalk or

hypophyseal stalk. Pituitary gland is divided into two called

1. The anterior pituitary (adenohypophysis)

2. The posterior pituitary (neurohypophysis).

In between these two divisions, there is a small and relatively avascular structure
called pars intermedia. In fact, it forms a part of the anterior pituitary.

Anterior pituitary is ectodermal in origin and arises from the pharyngeal

epithelium as an upward growth known as Rathke pouch.

Posterior pituitary is neuroectodermal in origin and arises from hypothalamus as

a downward diverticulum. Rathke pouch and the downward diverticulum from
hypothalamus grow towards each other and meet in the midway between the
roof of the buccal cavity and base of brain. There, the two structures lie close
together.

The relationship between hypothalamus and pituitary gland is called

hypothalamo-hypophyseal relationship. Hormones from hypothalamus are
transported to anterior pituitary through hypothalamo-hypophysial portal blood
vessels, while to posterior pituitary by nerve fibers of hypothalamo-hypophyseal
tract.

Blood supply: The primary blood supply to the pituitary gland arises from
the internal carotid arteries. The superior hypophyseal arteries supply the
pituitary infundibulum and, through the pituitary portal system, supply the
anterior pituitary gland while posterior pituitary blood supply is directly from the
inferior hypophyseal arteries. All these are branches of the posterior
communicating and internal carotid arteries.

Diagram showing the hypothalamus in relation to the pituitary gland

ANTERIOR PITUITARY

Location: It is the front lobe of the pituitary gland which is a small pea-sized gland
located at the base of the brain below the hypothalamus.

Structure: The anterior pituitary is referred to as the master gland because it

regulates many other endocrine glands via its hormone. It consists of three parts
namely

1. Pars distalis
2. Pars tuberalis
3. Pars intermedia

Pars Distalis: This is located at the distal part of the gland, and most of the
hormones get secreted from this region. It forms the major bulk of the anterior
pituitary. It is composed of follicles of varied sizes.
Pars Tuberalis: The tubular stalk is divided into pars tuberalis anteriorly and
posteriorly. It extends from the pars distalis. The pars tuberalis encircles the
infundibular stem, which is composed of unmyelinated axons from the
hypothalamic nuclei. The hormones oxytocin and vasopressin accumulate in these
axons, forming ovoid eosinophilic swellings along the infundibular stem. They
make up the ‘herring bodies.’

Pars Intermedia: This is present between the pars distalis and the posterior
pituitary gland. It is made up of follicles containing a colloidal matrix and includes
the remainder of the Rathke's pouch cleft. Though it is mostly nonfunctioning,
they produce melanocyte-stimulating hormones, endorphins and have some
pituitary stem cells.

Microscopic anatomy/histology of the anterior pituitary

The cells of the anterior pituitary of two types namely:

1. Chromophobe
2. Chromophil

These cells have staining properties.

Chromophobe cells: They have few granules with poor staining property. They
are not secretory in nature but are precusors for the chromophil cells.

Chromophil cells: They possess a large number of granules and are darkly stained.
These cells can be grouped in to two; based on their staining property and based
on their secretory nature.

1. Based on their staining property

a. Acidophilic cells or alpha cells e.g somatotropes and lactotropes
b. Basophilic cells or beta cells e.g corticotropes, thyrotropes,
gonadotropes and lactopes
2. Based on their secretory nature
a. Somatotropes (secretes growth hormone)
b. Corticotropes (secretes adrenocorticotropic hormone)
c. Thyrotropes (secretes TSH)
 d. Gonadotropes (secretes FSH and LH)
e. Lactotropes (prolactin)

Somatotropes and lactotropes are acidophilic cells, whereas others are basophilic
cells. Pituitary tumors that secrete large quantities of human growth hormone are
called acidophilic tumors.

Hypothalamic regulation of the anterior pituitary gland: The secretory function

of the anterior pituitary is regulated by the neurohormones secreted by the
hypothalamus. Special nerve cells in the hypothalamus synthesize and secretes
these neurohormones into median eminence and tuber cinereum. From here,
these hormones are transported by blood via hypothalamo-hypophyseal portal
vessels to the anterior pituitary to stimulate or inhibit secretions in the anterior
pituitary.

Hormones/Secretions of the anterior pituitary: These are

1. Growth hormone (GH) or somatotropic hormone (STH)

2. Thyroid-stimulating hormone (TSH) or thyrotropic hormone
3. Adrenocorticotropic hormone (ACTH)
4. Follicle-stimulating hormone (FSH)
5. Luteinizing hormone (LH) in females or interstitial cell-stimulating hormone
(ICSH) in males
6. Prolactin.
7. β-lipotropin

The first five hormones of anterior pituitary (as listed above) stimulates the other
endocrine glands. Growth hormone also stimulates the secretory activity of liver
and other tissues. Therefore, these five hormones are called tropic hormones.
Follicle-stimulating hormone and the luteinizing hormone are together called
gonadotropic hormones or gonadotropins because of their action on gonads

1. GH or STH: it is protein in nature, has a half-life of 20minutes in blood and is

degraded in the liver and kidneys.
Function: It is responsible for the general growth of the body. GH is
responsible for the growth of almost all tissues of the body, which are
capable of growing. It increases the size and number of cells by mitotic
division. GH also causes specific differentiation of certain types of cells like
bone cells and muscle cells. GH also acts on the metabolism of all the three
major types of foodstuffs in the body, viz. proteins, lipids and
carbohydrates.
Regulation: The secretion of GH is regulated by two releasing hormones
from the hypothalamus. Growth hormone– releasing hormone (GHRH),
which increases the secretion of GH, is produced during hypoglycemia,
exercise, fasting, stress, trauma, and initial stages of sleep. Another
stimulus for GHRH is a high blood level of amino acids; the GH then
secreted will ensure the conversion of these amino acids into protein.
Somatostatin may also be called growth hormone inhibiting hormone
(GHIH), and, as its name tells us, it decreases the secretion of GH.
Somatostatin is produced during hyperglycemia, increase in free fatty acid
in the blood and the later stages of sleep. GH secretion is under negative
feedback control.

Regulation of growth hormone

Applied physiology: Hypersecretion of GH causes enormous growth of the
body, leading to gigantism. Deficiency of GH in children causes stunted
growth, leading to dwarfism. In an adult, hypersecretion of GH is caused by
a pituitary tumor, and results in acromegaly. The long bones cannot grow
because the epiphyseal discs are closed, but the growth of other bones is
stimulated. The jaw and other facial bones become disproportionately
large, as do the bones of the hands and feet. The skin becomes thicker, and
the tongue also grows and may protrude. Other consequences include
compression of nerves by abnormally growing bones and growth of the
 articular cartilages, which then erode and bring on arthritis. Treatment of
acromegaly requires surgical removal of the tumor or its destruction by
radiation.
2. TSH: Thyroid-stimulating hormone is a peptide hormone with one α-chain
and one β-chain. Half-life of TSH is about 60 minutes. It is synthesised by
the anterior pituitary. Its release is stimulated by TRH from the
hypothalamus. Release is lowest in the early evening and highest during the
night.
Function: It stimulates growth and activity of the thyroid gland, which
secretes the hormones thyroxine (T4) and triiodothyronine (T3).
Regulation: Secretion is regulated by a negative feedback mechanism.
When the blood level of thyroid hormones is high, secretion of TSH is
reduced, and vice versa.
3. ACTH: ACTH is a single chained polypeptide with 39 amino acids. Half-life of
ACTH is 10 minutes. It stimulates the secretion of cortisol and other
hormones by the adrenal cortex.
Function: ACTH is necessary for the structural integrity and secretory
activity of adrenal cortex. It has other functions such as mobilization of fat
from tissues and melanocyte-stimulating effect i.e causing the darkening of
skin by acting cutaneous cells containing melanin.
Regulation: The hypothalamus stimulates the secretion of ACTH by
secreting CRF. CRF secretion is induced by any type of physiological stress
such as emotion, exercise,fever, trauma, hunger (this could be very
stressful) and circadian rhythm. CRF in turn, causes release of ACTH, which
induces glucocorticoid secretion. Its secretion can also be regulated by
negative feedback mechanism.
4. FSH: Follicle-stimulating hormone is one of the gonadotropic hormones;
that is, it has its effects on the gonads: the ovaries or testes. It is a
glycoprotein made up of one α-subunit and a β-subunit. The α-subunit has
92 amino acids and β-subunit has 118 amino acids. The half-life of FSH is
about 3 to 4 hours.
Functions: In males, FSH acts along with testosterone and accelerates the
process of spermeogenesis. In females FSH stimulates the growth of
 ovarian follicles (present in the ovaries); that is, it initiates egg development
in cycles of approximately 28 days, stimulates secretion of oestrogen by
follicle cells and promotes the aromatase activity in granulosa cells (one
type of cell of the ovaries), resulting in conversion of androgens into
estrogen.
Regulation: The secretion of FSH is stimulated by the hypothalamus, which
produces gonadotropin-releasing hormone (GnRH). FSH secretion is
decreased by inhibin, a hormone produced by the ovaries or testes.
5. LH or ICSH: LH is another gonadotropic hormone. LH is a glycoprotein made
up of one α-subunit and one β-subunit. The α-subunit has 92 amino acids
and β-subunit has 141 amino acids. The half-life of LH is about 60 minutes.
Function: In males, LH is known as interstitial cell-stimulating hormone
(ICSH) because it stimulates the interstitial cells of Leydig in testes to
secrete testosterone.
In females, In conjunction with FSH,causes the maturation of vesicular
follicle into graafian follicle. It is also responsible for ovulation (release of
mature ovum from ovarian follicle), formation of corpus luteum and
stimulation of the corpus luteum to secrete oestrogen and progesterone.
Regulation: The presence of oestrogen and progesterone in the blood
suppresses the secretion of LH. Its secretion is also regulated by GnRH from
the hypothalamus.
6. Prolactin: Prolactin is a single chain polypeptide with 199 amino acids. Its
half-life is about 20 minutes.
Function: Prolactin acts directly on the epithelial cells of mammary glands
and causes localized alveolar hyperplasia thus participating in the growth of
the mammary gland during pregnancy. It is also involved in the production
and secretion of milk after birth (lactation).
Regulation: the secretion of prolactin is regulated by PRH and PIH or
dopamine produced by the hypothalamus as well as increased blood levels
of prolactin (negative feedback mechanism). In conjunction with thyroxine,
insulin, corticosteroids and oestrogen, prolactin is involved in the initiating
and maintaining lactation.
Its production is increased during any period of sleep and emotional stress.
 7. β-lipotropin: β-lipotropin is a polypeptide hormone with 31 amino acids.
Function: It mobilizes fat from adipose tissue and promotes lipolysis. It also
forms the precursor of endorphins. This hormone acts through the adenyl
cyclase.

POSTERIOR PITUITARY

Location: it lies just below the hypothalamus. It is actually a part of the brain, an
extension of the hypothalamus containing a collection of axonal projections from
the hypothalamus that terminates behind the anterior pituitary.

Structure: Posterior pituitary consists of three parts:

1. Pars nervosa or infundibular process.

2. Neural stalk or infundibular stem.
3. Median eminence.

Pars tuberalis of anterior pituitary and the neural stalk of posterior pituitary
together form the hypophyseal stalk.

Microscopic anatomy/Histology of the posterior pituitary

Posterior pituitary is made up of neural type of cells called pituicytes and

unmyelinated nerve fibers. It also has numerous blood vessels, hyaline bodies,
neuroglial cells and mast cells.

Pituicytes: These are supporting cells derived from glial cells that do not secrete
any hormone.

Umyelinated nerve fibers: These come from supraoptic and paraventricular

nuclei of the hypothalamus through the pituitary stalk.

Diagram showing the hypothalamo-hypophyseal tract and the nuclei of the

posterior pituitary gland
Hormones/Secretions of the posterior pituitary: the posterior pituitary do not
actually secrete hormones but release hormones secreted by the hypothalamus.
These hormones are

1. Oxytocin
2. Antidiuretic hormone (ADH) or Vasopressin

These hormones are attached to carrier proteins called neurophysins and then
transported from the hypothalamus to the posterior pituitary through the nerve
fibers of hypothalamo-hypophyseal tract (by axonic flow). These hormones are
then stored in the nerve endings at the posterior pituitary and are released by
these nerve endings upon stimulation thus they are called neurohormones.

1. Oxytocin: It is mainly secreted by paraventricular nucleus of the

hypothalamus. A little amount is secreted by the supraoptic nucleus of the
hypothalamus. Oxytocin is a polypeptide having 9 amino acids. It has a half-
life of about 6 minutes.
 Function: In males, the release of oxytocin increases during ejaculation. It
facilitates release of sperm into urethra by causing contraction of smooth
muscle fibers in reproductive tract, particularly vas deferens.
In females, oxytocin acts on mammary glands and uterus of both pregnant
and non-pregnant women.
The action of oxytocin on non-pregnant uterus is to facilitate the transport
of sperms through female genital tract up to the fallopian tube, by
producing the uterine contraction during sexual intercourse. On pregnant
uterus, oxytocin causes contraction of uterus and helps in the expulsion of
fetus while its action on the mammary gland is milk ejection.
During sexual intercourse, at the onset of labor and suckling, receptors in
the vagina, the cervix and around the nipples respectively discharge
impulses that are sent via somatic afferent nerve fibres to the
paraventricular and supraoptic nuclei of the hypothalamus thus stimulating
these nuclei to secrete oxytocin that is sent to the posterior pituitary that
releases the oxytocin which causes the contraction of the uterus during
labor, contraction of the uterus towards the fallopian tube during coitus
and contraction of myoepithelial cells of the mammary glands (resulting in
ejection of milk from mammary glands) respectively. These responses
further stimulates the secretion of more oxytocin thus the secretion of
oxytocin uses positive feedback mechanism.
Stimulation of the uterus and milk ejection reflex by oxytocin are
neuroendocrine reflexes.
Regulation: It is regulated by hypothalamus using positive feedback
mechanism. Sensitivity of uterus to oxytocin is accelerated by estrogen and
decreased by progesterone.
2. ADH or Vasopressin: Antidiuretic hormone (ADH) is secreted mainly by
supraoptic nucleus of hypothalamus. A small amount is also secreted by the
paraventricular nucleus of the hypothalamus. Antidiuretic hormone is a
polypeptide containing 9 amino acids. Its half-life is 18 to 20 minutes.
Functions: the functions of ADH are retention of water (antidiuretic effect)
and vasoconstriction (vasopressor action).
 It increases the reabsorption of water by kidney tubules (distal convulated
tubule and collecting duct), which decreases the amount of urine formed.
In the absence of ADH, dilute urine is excreted thus large amount of water
is lost in urine which occurs in a condition called diabetes insipidus.
Excretion of large amount of water is called diuresis.
In large amounts, ADH causes vasoconstriction of all the arteries of the
body which leads to an increase in blood pressure.
However, the amount of ADH required to cause the vasopressor effect is
greater than the amount required to cause the antidiuretic effect.
Regulation: ADH secretion depends upon the volume of body fluid and the
osmolarity of the body fluids. Decrease in the extracellular fluid (ECF)
volume and an increase in osmolar concentration in the ECF stimulates ADH
secretion.

Diagram showing the anatomy of the pituitary gland

 APPLIED PHYSIOLOGY – DISORDERS OF PITUITARY GLAND

HYPERACTIVITY OF ANTERIOR PITUITARY

1. Gigantism: this is characterized by excess growth of the body where the

subject looks like giants of about 7- 8 feet in height.
Causes: tumor of the acidophil cells of the anterior pituitary which leads to
hypersecretion of GH in children or pre-adults before the fusion of the
epiphysis of bone with shaft.
Signs and symptoms: general overgrowth, limbs are disproportionately
long, visual disturbances due to compression of the fibres of the optic
chiasma, hyperglycemia due to degeneration of insulin producing cells as a
result of overstimulation leading to insulin deficiency.
2. Acromegaly: this is characterized by the enlargement, thickening and
broadening of bones, particularly in the extremities of the body.
Causes: tumor of acidophil cells of the anterior pituitary (which leads to
hypersecretion of GH) in adults or after the the fusion of the epiphysis with
the bone.
Signs and symptoms: gorilla face (thick lips, very broad nose, lower jaw
protrusion etc), enlarged hands and feet, kyphosis, over grown body hairs,
enlarged visceral organs, thick scalp, hypertension, headache, visual
disturbances, hyperactivity of thyroid, parathyroid and adrenal glands etc
3. Acromegalic Gigantism: Acromegalic gigantism is a rare disorder with sym
ptoms of both gigantism and acromegaly. Hypersecretion of GH in children,
before the fusion of epiphysis with shaft of the bones causes gigantism and
if hypersecretion of GH is continued even after the fusion of epiphysis, the
symptoms of acromegaly also appear.
4. Cushing disease: this is characterized by obesity.
Causes: tumor of basophilic cells of the anterior pituitary It increases the
secretion of adrenocorticotropic hormone, which in turn stimulates the
adrenal cortex to release cortisol. It can also be caused by tumor in the
adrenal gland, this type is called Cushing syndrome.
 HYPOACTIVITY OF ANTERIOR PITUITARY
1. Dwarfism: This is a pituitary disorder in children, characterized by the
stunted growth.
Causes: Reduction in GH secretion in infancy or early childhood due to
tumor of chromophobes (most common), deficiency in GHRH and
somatomedin C secretion, atrophy (degeneration) of acidophilic cells and
panhypopituitarism (reduction in the secretion of all anterior pituitary
hormones).
Signs and symptoms: stunted skeletal growth and unattainment of puberty
in the case of panhypopituitarism because reduced secrecretion of
gonadotropins if not no other part of the body is actually affected.
Read up the following : Laron dwarfism, Psychogenic dwarfism, frohlich’s
syndrome.
2. Acromicria: This is a rare disease in adults characterized by the atrophy of
the extremities of the body.
Causes: Deficiency of GH in adults due to to tumor of chromophobes,
deficiency in GHRH secretion, degeneration of acidophilic cells and
panhypopituitarism.
Signs and symptoms: Atrophy and thinning of extremities of the body, loss
of sexual function, lethargy, obesity, hypothyroidism etc
3. Simmond disease: This is a rare pituitary disease. It is also called pituitary
cachexia.
Causes: It occurs mostly in panhypopituitarism, i.e. hyposecretion of all the
anterior pituitary hormones due to the atrophy or degeneration of anterior
pituitary
Signs and symptoms: rapidly developing senile decay (situations where a
20year old looks like a 40 year old) is the most common feature of this
disease, loss of hair over the body and loss of teeth, skin on face becomes
dry and wrinkled etc.
HYPOACTIVITY OF POSTERIOR PITUITARY

1. Diabetes insipidus: This is a posterior pituitary disorder characterized by

excess excretion of water through urine.
Causes: Deficiency of ADH due to Lesion (injury) or degeneration of
supraoptic and paraventricular nuclei of hypothalamus or the
hypothalamo-hypophyseal tract or the posterior pituitary or the inability of
renal tubules to give response to ADH hormonein which case it is referred
to as nephrogenic diabetes insipidus.
Signs and symptoms: polyuria (excretion of large quantity of dilute urine,
with increased frequency of voiding), polydipsia (Intake of excess water)
and dehydration in some cases where the lesion affected the thirst centre
in the hypothalamus.

N.B: nephrogenic diabetes insipidus is a genetic disorder caused by the

mutation of genes which affects receptors responsible for reabsorption of water
in the distal convulated tubule and collecting duct.

Assignment

Read up: Dystrophia adiposogenitalis or hypothalamic eunuchism (hypoactivity of

both anterior and posterior pituitary).
 THE THYROID GLAND

The thyroid gland weighs about 20 - 40 g in adults. It is larger in females than in

males.The structure and the function of the thyroid gland change in different
stages of the sexual cycle in females. Its function increases slightly during
pregnancy and lactation and decreases during menopause.

Location: It situated at the root of the neck on either side of the trachea at the
level of C5-T1.

Structure: It has two lobes, which are connected in the middle by an isthmus. The
structural units of the thyroid gland are thyroid follicles. The thyroid gland is
composed of large number of closed follicles. These follicles are lined with
cuboidal epithelial cells, which are called the follicular cells. These follicular cells
secretes thyroglobulin, a colloidal substance that fills up the follicular cavity.
These cells also secrete tetraiodothyronine (T4 or thyroxine) and tri-
iodothyronine (T3 ). Parafollicular cells (or C-cells) present between the follicles
secretes calcitonin.
Two parathyroid glands lie against the posterior surface of each lobe and are
sometimes embedded in thyroid tissue.
Regulation: Hypothalamus regulates thyroid secretion by controlling TSH
secretion through thyrotropic-releasing hormone (TRH). From hypothalamus, TRH
is transported through the hypothalamo-hypophyseal portal vessels to the
anterior pituitary. After reaching the pituitary gland, the TRH causes the release of
TSH.

Thyroid hormones also regulate their own secretion through negative feedback
control, by inhibiting the release of TRH from hypothalamus and TSH from
anterior pituitary.

Iodide is another important factor regulating the synthesis of thyroid hormones.

When the dietary level of iodine is moderate, the blood level of thyroid hormones
is normal. However, when iodine intake is high, the enzymes necessary for
synthesis of thyroid hormones are inhibited by iodide, resulting in suppression of
hormone synthesis. This effect of iodide is called Wolff Chaikoff effect.

Many other factors are involved in the regulation of thyroid secretion in

accordance to the needs of the body. Stimulatory factors include low BMR,leptin
(from adipose tissue), α-melanocyte-stimulating hormone (from the pituitary) and
low temperature (only in infants). Inhibitory factors include excess iodide intake,
stress, somatostatin, glucocorticoids and dopamine. These inhibitory factors
perform their action by inhibiting the secretion of TRH.

Blood supply: The arterial blood supply to the gland is through the superior and
inferior thyroid arteries. The superior thyroid artery is a branch of the external
carotid artery and the inferior thyroid artery is a branch of the subclavian artery.
The venous return is by the thyroid veins which drain into the internal jugular
veins.

Hormones of the thyroid gland: These are

1. Tetraiodothyronine or T4 (thyroxine or tetra-iodothyronine)

2. Tri-iodothyronine or T3
3. Calcitonin.

1. Thyroid Hormones (T3 and T4)

Both T4 and T3 are iodine-containing derivatives of amino acid tyrosine with T4

forming about 90% and T3 about 10%.Thyroid hormones have long half-life. T4 has
a long half-life of 7 days. Half-life of T3 is varies between 10 - 24 hours. The
potency of T3 is four times more than that of T4 . T4 acts for longer period than T3.
Duration of T4 action is four times more than T3 action. This is because of the
difference in the affinity of these hormones to plasma proteins. T 3 has less affinity
for plasma proteins and combines loosely with them, so that it is released quickly.
T4 has more affinity and strongly binds with plasma proteins, so that it is released
slowly. Therefore, T3 acts on the target cells immediately and T4 acts slowly.
Thyroid hormones are degraded in the muscles, liver and kidney.

Synthesis: Synthesis of thyroid hormones takes place in thyroglobulin, present in

follicular cavity. Iodine and tyrosine are essential for the formation of thyroid
hormones. Iodine and tyrosine are consumed through diet. Iodine is converted
into iodide,then iodide and tyrosine are absorbed from the GI tract. To prevent
iodine deficiency, common table salt is iodized with one part of sodium iodide to
every 100,000 parts of sodium chloride.

Synthesis of thyroid hormones occurs in five stages:

 1. Thyroglobulin synthesis which occurs in the endoplasmic reticulum and
golgi apparatus in the follicular cells of thyroid gland.
2. Iodide trapping which means active transportation of iodide from blood to
follicular cells.
3. Oxidation of iodide to iodine because only iodine can combine with
tyrosine to form thyroid hormone in the presence of thyroid peroxidase.
4. Transport of iodine into follicular cavity by an iodide-chloride pump called
pendrin.
5. Iodination of tyrosine facilitated by iodinase secreted by follicular cells.
Iodination of tyrosine occurs in several stages. Tyrosine is iodized first into
monoiodotyrosine (MIT) and later into di-iodotyrosine (DIT). MIT and DIT
are called the iodotyrosine residues.
6. Coupling reactions which involves iodotyrosine residues getting coupled
with one another.
Tyrosine + I = Monoiodotyrosine (MIT)
MIT + I = Di-iodotyrosine (DIT)
DIT + MIT = Tri-iodothyronine (T3 )
MIT + DIT = Reverse T3
DIT + DIT = Tetraiodothyronine or Thyroxine (T4 )

In combination with thyroglobulin, the thyroid hormones can be stored for

several months. Thyroid gland is unique in this, as it is the only endocrine gland
that can store its hormones for a long period of about 4 months. So, when the
synthesis of thyroid hormone stops, the signs and symptoms of deficiency do not
appear for about 4 months.

Thyroglobulin itself is not released into the bloodstream. On the other hand, the
hormones are first cleaved from thyroglobulin and released into the blood.

MIT and DIT are not released into blood. These iodotyrosine residues are
deiodinated by an enzyme called iodotyrosine deiodinase, resulting in the release
of iodine. The iodine is reutilized by the follicular cells for further synthesis of
thyroid hormones. During congenital absence of iodotyrosine deiodinase, MIT and
DIT are excreted in urine and the symptoms of iodine deficiency develop.

Thyroid hormones are transported in the blood by three types of proteins called
thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA) and
albumin.

Functions: Thyroid hormones have two major effects on the body which are to
increase basal metabolic rate and to stimulate growth in children. The actions of
thyroid hormones are

i. increase in metabolic activities of most tissues in the body except brain,

spleen, retina, testis and lungs.
ii. Increase in the synthesis of protein in cells.
iii. Stimulation of all processes involved in carbohydrate metabolism
iv. Decrease in fat storage thus increasing free fatty acid levels in blood
v. Helps maintain body weight
vi. Increase in the overall activity of cardiovascular system
vii. Acceleration of erythropoietic activity and increase in blood volume.
viii. Increase in the formation of many enzymes.
ix. Increase in heat production in the body, by accelerating various cellular
metabolic processes and increasing BMR.
x. Acceleration of growth in the body, especially in growing children
xi. Indirect increase in the rate and force of respiration
xii. increases the appetite and food intake. It also increases the secretions
and movements of GI tract.
xiii. Maintenance of normal sleep pattern.
xiv. Increase in the demand for secretion by other endocrine glands.

Regulation: hypothalamic regulation, negative feedback mechanism and

iodide (refer to the regulation of the thyroid gland secretions).
 2. Calcitonin

Calcitonin is a polypeptide chain with 32 amino acids. It is synthesized from

procalcitonin and has a half life of 5-10 minutes. It is degraded and excreted by
liver and kidney.
Function: the two major functions of calcitonin is to decrease blood calcium
(counteracts parathyroid hormone action) and blood phosphate (works in synergy
with parathyroid hormone)levels. This function of calcitonin helps maintain
normal blood levels of calcium and phosphate and also helps maintain a stable,
strong bone matrix.

It decreases blood calcium levels by the following ways:

i. Stimulates osteoblastic activity and facilitates the deposition of calcium

on bones.
ii. suppresses the activity of osteoclasts and inhibits the resorption of
calcium from bones.
iii. inhibits even the development of new osteoclasts in bones
iv. increases excretion of calcium through urine, by inhibiting the
reabsorption from the renal tubules
v. prevents the absorption of calcium from intestine into the blood.

It decreases blood phosphate by the following ways:

i. inhibits the resorption of phosphate from bones.

ii. stimulates the deposition of phosphate on bones.
iii. increases the excretion of phosphate through urine, by inhibiting the
reabsorption from renal tubules.

Regulation: secretion of calcitonin is stimulated by high plasma levels of calcium

and gastrin.

APPLIED PHYSIOLOGY – DISORDERS OF THYROID GLAND

1. Hyperthyroidism: increased secretion of thyroid hormone.

Causes: . Graves’ disease (autoimmune disease) and thyroid adenoma (tumor in

the thyroid tissue).

Signs and symptoms: Intolerance to heat as the body produces lot of heat due to
increased basal metabolic rate caused by excess of thyroxine, increased sweating
due to vasodilatation, decreased body weight due to fat mobilization, diarrhea
due to increased motility of GI tract, muscular weakness because of excess
protein catabolism, cardiac failure, amenorrhea, tachycardia, polycythemia,
nervousness, extreme fatigue, inability to sleep, mild tremor in the hands and
psychoneurotic symptoms such as hyperexcitability, extreme anxiety or worry due
to the excess stimulation of neurons in the central nervous system etc

Treatment: using antithyroid substances or surgical removal.

2. Hypothyroidism: decreased secretion of thyroid hormones. It leads to

myxedema in adults and cretinism in children.

i. Myxedema: characterized by edematous appearance

Causes: diseases of thyroid gland, genetic disorder, iodine deficiency or deficiency

of TRH and/or TSH.

Signs and symptoms: swelling of the face, bagginess under the eye, anaemia,
Frog-like husky voice, cold intolerance, increase in body weight, constipation etc.

ii. Cretinism: characterized by stunted growth.

Causes: congenital absence of thyroid gland, genetic disorder or lack of iodine in

the diet.

Sign and symptoms: sluggish movements, croaking crying sound, large tongue,
mental retardation etc

Treatment: treatment for hypothyroidism is the administration of thyroid extract

or ingestion of pure thyroxine in the form of tablets, orally.

NB: mental retardation and disproportionate body parts are the major difference
between dwarfism and cretinism.

3. Goiter: enlargement of the thyroid gland which can occur in

hyperthyroidism(toxic goiter) and hypothyroidism (non-toxic goiter).
 THYROID FUNCTION TESTS

Functional status of thyroid gland is assessed by the following tests:

i. Measurement of plasma level of T3 and T4 : For hyperthyroidism or

hypothyroidism, the most accurate diagnostic test is the direct
measurement of concentration of “free” thyroid hormones in the
plasma, i.e. T3 and T4 .
ii. Measurement of TRH and TSH: There is almost total absence of these
two hormones in hyperthyroidism. It is because of negative feedback
mechanism, by the increased level of thyroid hormones.
iii. Measurement of basal metabolic rate: In hyperthyroidism, basal
metabolic rate is increased by about 30% to 60%. Basal metabolic
rate is decreased in hypothyroidism by 20% to 40%.
 PARATHYROID GLAND

Humans posses four parathyroid glands which are very small in size and dark
brown in colour measuring about 6 mm in length, 3 mm in width and 2 mm thick.

Location: It situated on the posterior surface of upper and lower poles of thyroid
gland.

Structure: Each parathyroid gland is made up of chief cells and oxyphil cells. Chief
cells secrete parathormone. Oxyphil cells are the degenerated chief cells and their
function is known. However, these cells may secrete parathormone during
pathological condition called parathyroid adenoma. The number of oxyphil cells
increases after puberty.

Blood supply: The vascular supply is similar to that of the thyroid gland.

Arterial supply is chiefly via the inferior thyroid artery (as this artery supplies the
posterior aspect of the thyroid gland – where the parathyroids are located).
Collateral arterial supply is from the superior thyroid artery and thyroid ima
artery. Venous drainage is into the superior, middle, and inferior thyroid veins

Hormones/Secretion of the parathyroid gland: Parathormone is the hormone

secreted by the parathyroid gland.

Parathyroid Hormone

It is a protein hormone with 84 amino acid molecule. It has a half-life of 10

minutes.

This hormone is essential for the maintenance of blood calcium level within a very
narrow critical level. Maintenance of blood calcium level is necessary because
calcium is an important inorganic ion for many physiological functions such as
muscle contraction, blood clotting, nerve impulse transmission etc

Parathormone is synthesized from the precursor called prepro-PTH (115 amino

acids), then it is enters the endoplasmic reticulum of chief cells of parathyroid
glands where it is converted into a prohormone called pro-PTH (96 amino acids),
then it moves to the Golgi apparatus, where it is converted into PTH.

PTH is mainly degraded by Kupffer cells of liver, by means of proteolysis. PTH is

also degraded by the kidney (20-30%).

Functions: The primary function of PTH is to maintain the blood calcium level
within the critical range of 9 to 11 mg/dL and it does this by acting on bone,
kidney and the GIT. It also helps maintain blood phosphate level.

PTH increases blood calcium level in the following ways:

 i. It enhances the resorption of calcium from the bones (osteoclastic
activity) by acting on osteoblasts and osteoclasts of the bone.
ii. It increases the reabsorption of calcium from the renal tubules (distal
convulated tubule and proximal part of collecting duct) along with
magnesium ions and hydrogen ion in the kidney.
iii. It also increases the formation of 1,25- dihydroxycholecalciferol
(activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.
iv. It increases the absorption of calcium ions from the GI tract indirectly by
activating vitamin D in the liver and kidney, the activated vitamin D
facilitates the absorption of calcium in the GIT.

The overall effect of PTH on blood phosphate level is to reduce blood phosphate
level and it achieves this in the following ways:

i. PTH also increases phosphate absorption from the bones along with
calcium resorption.
ii. It increases the absorption of phosphate from GI tract through calcitriol
(activated vitamin D3).
iii. PTH increases phosphate excretion (more than is obtained from bones)
by inhibiting reabsorption of phosphate from renal tubules (proximal
convoluted tubule).

Regulation: Blood level of calcium is the main factor regulating the secretion of
PTH. Blood phosphate level also regulates PTH secretion. Secretion of PTH is
stimulated by hypocalcemia, a low blood calcium level, and inhibited by
hypercalcemia.

Increase in blood calcium level decreases PTH secretion. PTH secretion decreases
in conditions such as excess consumption of calcium in the diet, increased vitamin
D intake in food and increased resorption of calcium from the bones, caused by
bone diseases or other factors.

Decrease in blood calcium level increases PTH secretion. PTH secretion increases
in conditions such as pregnancy, rickets, and lactation.
PTH secretion in response to phosphate level is indirect as an increased blood
phosphate level will lead to the binding of phosphate to ionized calcium to form
calcium hydrogen phosphate making calcium level in the blood to decrease, and a
decrease in blood calcium level stimulates PTH secretion which would inturn
decrease phosphate in circulation.

As you might expect, a sustained hypersecretion of PTH, such as is caused by a

parathyroid tumor, would remove calcium from bones and weaken them. It has
been found, however, that an intermittent, brief excess of PTH, such as can occur
by injection, will stimulate the formation of more bone matrix, rather than matrix
reabsorption. This may seem very strange—the opposite of what we would
expect—but it shows how much we have yet to learn about the body. PTH is
being investigated as a possible way to help prevent osteoporosis.

DISORDERS OF PARATHYROID GLANDS

Disorders of parathyroid glands are of two types:

I. Hypoparathyroidism
II. Hyperparathyroidism

1. Hypoparathyroidism: this is the hyposecretion of PTH which invariably

leads to hypocalcemia.
Causes: Surgical removal of parathyroid glands (parathyroidectomy),
removal of parathyroid glands during surgical removal of thyroid gland
(thyroidectomy), autoimmune disease and deficiency of receptors for PTH
in the target cells. In this, the PTH secretion is normal or increased but the
hormone cannot act on the target cells. This condition is called
pseudohypoparathyroidism.
Signs and symptom: these are usually due to hypocalcemia elicited by
hypoparathyroidism. Hypocalcelmia leads to hyperexcitability of nerves and
skeletal muscle. These signs/symptoms are tetany (characterized by painful
 muscular spasm which are involuntary muscle contractions), hyper-reflexia
(overactive reflex actions), convulsions, carpopedal spasms (spasms of
hands and feet), laryngeal stridor which noisy inspiration sound due to
laryngeal spasms, hypotension, heart failure, dry skin, brittle nails, hair loss,
mental retardation in children or dementia in adults etc

2. Hyperparathyroidism: this is the hypersecretion of parathormone which

leads to hypercalcemia. Hyperparathyroidism is of three types namely
primary, secondary and tertiary hyperparathyroidism.
Causes:
Primary hyperparathyroidism: this is due to the development of tumor in
one or more parathyroid glands.
Secondary hyperparathyroidism: this is due to the physiological
compensatory hypertrophy (increase in the mass of individual cells) of
parathyroid glands, in response to hypocalcemia which occurs due to other
pathological conditions such as chronic renal failure, vitamin D deficiency,
or rickets etc.
Tertiary hyperparathyroidism: this is due to hyperplasia (abnormal
increase in the number of cells) of all the parathyroid glands that develops
due to chronic secondary hyperparathyroidism.
Signs and symptoms: sluggishness of reflex activities, depression of the
nervous system, lack of appetite, constipation, parathyroid poisoning, renal
stones etc
 PANCREAS AS AN ENDOCRINE GLAND

The pancreas is an exocrine (digestive) gland as well as an endocrine gland but

only its endocrine structure and function will be explained here in the endocrine
system as its exocrine structure and function have been discussed under the GIT
or digestive system.

Location: The pancreas is located in the upper left quadrant of the abdominal
cavity, extending from the curve of the duodenum to the spleen.

Structure: The endocrine (hormone-producing) cells of the pancreas are called

islets of Langerhans (pancreatic cells) are found in clusters irregularly distributed
throughout the substance of the pancreas. There are about 1-2million of these
cells present in the human pancreas. These cells secrete pancreatic hormones
directly into the blood stream and is circulated all around the body. Islets of
Langerhans consist of four types of cells:

1. A cells or α-cells, which secrete glucagon.

2. B cells or β-cells, which secrete insulin
3. D cells or δ-cells, which secrete somatostatin.
4. F cells or PP cells, which secrete pancreatic polypeptide.

Blood supply: Pancreaticoduodenal, splenic, gastroduodenal, and superior

mesenteric arteries. The venous drainage of the duodeno-pancreas is effected via
a posterosuperior and an anteroinferior vein, the former draining toward the
portal vein and the second into the superior mesenteric vein

Hormones/secretions of the pancreas: these are;

1. Glucagon
2. Insulin
3. Somatostastatin
4. Pancreatic polypeptide.

1. Insulin
Insulin is a polypeptide with 51 amino acids secreted by β-cells in the islets of
Langerhans of pancreas. It is made up amino acid chains called α and β chains,
linked to each other by disulfide bridges consisting of 21 amino acids and 30
amino acids respectively. It has a half-life of 5 minutes.

Synthesis of insulin occurs in the rough endoplasmic reticulum of β-cells in islets

of Langerhans. It is synthesized as preproinsulin, that gives rise to proinsulin
which is then converted into insulin and C peptide through a series of peptic
cleavages. C peptide is a connecting peptide that connects α and β chains. At the
time of secretion, C peptide is detached.

Binding of insulin to insulin receptor is essential for its removal from circulation
and degradation. Insulin is degraded in liver and kidney by a cellular enzyme
called insulin protease or insulin-degrading enzyme.

Function: The primary function of insulin in the body is to decrease blood glucose
level. Other functions include stimulation of growth (in synergy with growth
hormone), protein and fat metabolism. Insulin carry these functions in the
following ways:

i. Facilitating transport and uptake of glucose by the cells by increasing the

permeability of the cell membrane to glucose.
ii. Increasing the peripheral utilization of glucose particularly by liver
tissues, muscle tissues and adipose tissues.
iii. Increasing the storage of glucose by converting it into glycogen in liver
and muscle.
iv. Inhibiting glycogenolysis (the breakdown of glycogen into glucose in
muscle and liver).
v. Inhibiting gluconeogenesis (the formation of glucose from proteins by
inhibiting the release of amino acids from muscle and by inhibiting the
activities of enzymes involved in gluconeogenesis).
vi. Insulin promotes the synthesis of lipids by activating the enzymes which
convert glucose into fatty acids and then these fatty acids into
triglycerides.
vii. Promoting transport of fatty acids into adipose tissue
 viii. Facilitating storage of fat by inhibiting the enzymes that breakdown
triglycerides.
ix. In synergy with growth hormone, promtes growth of the body by
enhancing amino acid transport into cells and protein synthesis within
the cell
x. It causes the conservation of protein by increasing the utilization of
glucose by cell. This what is referred to as protein-sparing effect of
insulin.

Regulation: insulin is mainly regulated by blood glucose level amongst other

factors such as protein, lipid derivatives, GI hormones, endocrine hormones and
nervous stimulation.

Stimulants of insulin secretion are hyperglycemia (increased blood glucose level),

excess amino acid in blood (slight effect without increase blood in glucose level),
β-ketoacids (lipid derivative), glucagon (indirectly by converting amino acid to
glucose etc), growth hormone, gastrin, secretin, cholecystokinin (CCK),
gastrointestinal peptide (GIP), parasympathetic nerve stimulation (via the vagus
nerve using acetycholine as its neurotransmitter).

Factors that inhibit the secretion of insulin are somatostatin (GHRIH) secreted by
cells of the pancreatic islets (similar to that produced by the hypothalamus),
glucagon, cortisol, adrenaline and sympathetic nerve stimulation.

2. Glucagon

Glucagon is not only secreted by the pancreas but also by the A cells of the
stomach and L cells of the small intestine. It is a polypeptide containing 29 amino
acid molecules. Its half-life ranges from 3 to 6minutes. It is synthesized from
preproglucagon in the A cells of the islet, the preproglucagon is converted to
proglucagon which finally converted to glucagon. It is degraded in blood (50%),
liver (30%) and kidney (20%).
Functions: The actions of glucagon are antagonistic to those of insulin. The overall
effect of glucagon is to raise the blood glucose level and to make all types of food
available for energy production and it achieves this aim by the following ways:

i. It increases glycogenolysis in liver (but not in muscles) and releases

glucose from the liver cells into the blood. This process is called
glycogenolysis.
ii. Increasing the transport of amino acids into the liver cells which are
utilized for glucose formation (gluconeogenesis).
iii. It shows lipolytic activity by promoting ketogenesis (formation of ketone
bodies) in liver.
iv. It increases lipolysis by increasing the release of free fatty acids from
adipose tissue and making them available for peripheral utilization.
v. It inhibits the secretion of gastric juice.
vi. It increases the secretion of bile from liver.

Regulation: Secretion of glucagon is controlled mainly by glucose and amino acid

levels in the blood.

Normal blood glucose level is 70 to 110 mg/dL, a decrease below this range will
stimulate glucagon synthesis and release while an increase above this range will
inhibit glucagon secretion. This same effect applies in the case of an increase or a
decrease in blood amino acid levels.

Other factors that stimulate glucagon secretion includes exercise, stress, gastrin,
cholecystokinin and cortisol.

Other factors that inhibit glucagon secretion are somatostatin, insulin, free fatty
acids and ketones.

3. Somatostatin

Other than the D cells in the islets of Langerhans of pancreas, the hypothalamus,
stomach and initial part of the small intestine (duodenum).

Somatostatin is a polypeptide. It is synthesized in two forms, namely

somatostatin-14 (with 14 amino acids) and somatostatin-28 (with 28 amino
acids). Both forms have similar function. Half-life of somatostatin is 2 to 4
minutes.

Somatostatin is synthesized from the precursor prosomatostatin. Prosomatostatin

is converted mostly into somatostatin-14 in the D cells of islets in pancreas.
However, in the intestine, large amount of somatostatin28 is produced from
prosomatostatin.

Somatostatin is degraded in liver and kidney.

Function: Its overall function is to counteract the effect of glucagon and insulin

i. Somatostatin acts within islets of Langerhans and, inhibits β and α cells,

i.e. it inhibits the secretion of both glucagon and insulin.
ii. It decreases the motility of stomach, duodenum and gallbladder.
iii. It reduces the secretion of gastrointestinal hormones gastrin, CCK, GIP
and VIP.
iv. Hypothalamic somatostatin inhibits the secretion of GH and TSH from
anterior pituitary. That is why, it is also called growth hormone-
inhibitory hormone (GHIH).

4. Pancreatic polypeptide

It is not only secreted by F cells or PP cells of pancreas as it can also be found in

the small intestine. It is a polypeptide with 36 amino acids. Its half-life is 5
minutes.

Pancreatic polypeptide is synthesized from preprohormone precursor called

prepropancreatic polypeptide in the PP cells of islets. It is degraded and removed
from circulation mainly in the kidney.

Function: Exact physiological action not known.

Regulation: Secretion of pancreatic polypeptide is stimulated by the presence of

chyme containing more proteins in the small intestine.
 BLOOD GLUCOSE LEVEL

In normal persons, blood glucose level is controlled within a narrow range. In the
early morning after overnight fasting, the blood glucose level is low ranging
between 70 and 110 mg/dL of blood. Between first and second hour after meals
(postprandial), the blood glucose level rises to 100 to 140 mg/dL. Glucose level in
blood is brought back to normal at the end of second hour after the meals. Blood
glucose regulating mechanism is operated through liver and muscle by the
influence of the pancreatic hormones – insulin and glucagon. Many other
hormones are also involved in the regulation of blood glucose level. Among all the
hormones, insulin is the only hormone that reduces the blood glucose level and it
is called the antidiabetogenic hormone. The hormones which increase blood
glucose level are called diabetogenic hormones or anti-insulin hormones e.g
growth hormone, thyroxine, Cortisol and adrenaline.

Regulation and maintenance of blood glucose level

Regulation of blood glucose (sugar) level is very essential because, glucose is the
only nutrient that is utilized for energy by many tissues such as brain tissues,
retina and germinal epithelium of the gonads.

The liver plays an important role in the regulation and maintenance of blood
glucose level as it serves as a buffer system. The liver helps to maintain the blood
glucose level by storing glycogen when blood glucose level is high after meals; and
by releasing glucose, when blood glucose level is low after 2 to 3 hours of food
intake. Insulin helps to control the blood glucose level, especially after meals,
when it increases. Glucagon and other hormones help to maintain the blood
glucose level by raising it in between the meals.

APPLIED PHYSIOLOGY

1. Diabetes mellitus: This is a metabolic disorder characterized by high blood

glucose level, associated with other manifestations. ‘Diabetes’ means
‘polyuria’ and ‘mellitus’ means ‘honey’. The name ‘diabetes mellitus’ was
coined by Thomas Willis, who discovered sweetness of urine from diabetics
in 1675. In most of the cases, diabetes mellitus develops due to deficiency
of insulin. There are several forms of diabetes mellitus, which occur due to
different causes. Diabetes may be primary or secondary. Primary diabetes
is unrelated to another disease. Secondary diabetes occurs due to damage
or disease of pancreas by another disease or factor. Recent classification
divides primary diabetes mellitus into two types, Type I and Type II.

Type I Type II

Previous names Insulin-dependent Non-insulin

DM or Juvenile dependent or adult
onset diabetes onset diabetes

Percentage of DM 5-10% 90-95%

cases

Age of occurrence Below 30yrs: usually Above 30yrs:

childhood or increasing in
adolescence or any childhood and
age following adolescence in
autoimmune association with
stimulus e.g virus obesity and
inactivity.

Onset Rapid Gradual

Primary etiology Autoimmune Genetic and

mediated environmental
mechanism with factors e.g family
genetic history, ethnicity,
predisposition obesity, inactivity
etc
Pathogenesis Destruction of beta Increasing resistance
cells with absolute of tissue (liver and
insulin deficiency muscle) to insulin),
and abnormal impaired
glucose control. (deficiency) insulin
secretion and
increase hepatic
glucose production

Signs and symptoms Polyuria, polydipsia, Polyuria, polydipsia,

polyphagia, polyphagia, obesity,
unexplained weight fatigue, blurred
loss, fatigue, blurred vision, possibly
vision, possible asymptomatic
ketoacidosis

Treatment Non-drug therapy Non-drug therapy

includes medical includes essential
nutrition therapy adjunct to anti-
and physical activity diabetic drugs may
approved by a be sufficient to
physician control blood
Drug therapy glucose level
includes insulin Drugs MNT
monotherapy or oral monotherapy or
anti-diabetic drugs oral diabetic drugs
in combination with or insulin therapy
insulin therapy if with anti-diabetic
insulin resistant. drugs etc
Diagnostic Tests for Diabetes Mellitus

i. Fasting blood glucose.

ii. Postprandial blood glucose.
iii. Glucose tolerance test (GTT).
iv. Glycosylated (glycated) hemoglobin.

2. Hyperinsulinism: This is the hypersecretion of insulin.

Causes: tumor of β-cells in the islets of Langerhans.

Signs and symptoms: Hypoglycemia (blood glucose level below 50 mg/dL) and
neuroglycopenic symptom (manifestations of the CNS associated with
hypoglycemia such as hyperactivity of the neurons leading to tremor,
convulsions and possibly coma).
 ADRENAL GLAND (SUPRARENAL GLAND)

Adrenal glands are called the ‘life-saving glands’ or ‘essential endocrine glands’. It
is because the absence of adrenocortical hormones causes death within 3 to 15
days and absence of adrenomedullary hormones, drastically decreases the
resistance to mental and physical stress. There are two adrenal glands.

The right gland is roughly triangular in shape, and the left, which is commonly the
larger of the two, is crescent‐shaped. Both glands are encased in a connective
tissue capsule and embedded in an area of fat. Adrenal glands are very vascular
(have a rich blood supply from many blood vessels)

Location: The two adrenal glands are located one on top of each kidney enclosed
in the renal fascia of the kidney, which gives them their other name, suprarenal
glands.

Structure: Each adrenal gland consists of two parts: an inner adrenal medulla
(20% of the gland) and an outer adrenal cortex (80% of the gland). The hormones
produced by each part have very different functions. These two parts are
different from each other in development, structure and functions. The adrenal
cortex is essential to life but the medulla is not. Adrenal medulla develops from
the neural crest, which gives origin to sympathetic nervous system. So, its
secretions and functions resemble that of sympathetic nervous system. Adrenal
cortex develops from the mesonephros, which give rise to the renal tissues. It
secretes entirely a different group of hormones known as corticosteroids.

Blood supply: The arterial blood supply to the glands is by branches from the
abdominal aorta and renal arteries. The venous return is by suprarenal veins. The
right gland drains into the inferior vena cava and the left into the left renal vein.
 ADRENAL CORTEX

Microscopic anatomy : Adrenal cortex is formed by three layers of structure. Each

layer is distinct from one another.

1. Outer zona glomerulosa.

2. Middle zona fasciculate.
3. Inner zona reticularis.
Hormones/secretions of the adrenal cortex: Adrenocortical hormones are
steroids in nature, hence the name ‘corticosteroids’ and are thus synthesized
mainly from cholesterol that is absorbed directly from the circulating blood. Small
quantity of cholesterol is also synthesized within the cortical cells from
acetylcoenzyme A (acetyl-CoA).

Corticosteroids are degraded mainly in the liver and conjugated to form

glucuronides and to a lesser extent, form sulfates. About 25% of corticosteroids
are excreted in bile and feces and remaining 75%, in the urine

Based on their functions, corticosteroids are classified into three groups:

1. Mineralocorticoids
2. Glucocorticoids
3. Sex hormones.

1. Mineralocorticoid: Mineralocorticoids are secreted by the zona

glomerulosa of adrenal cortex and are transported in blood by binding with
plasma proteins, especially globulins. The binding is loose and 50% of these
hormones are present in free form. They are the corticosteroids that act on
the minerals (electrolytes), particularly sodium and potassium Their half-life
is 20minutes. Mineralocorticoids are
i. Aldosterone and
ii. 11-deoxycorticosterone.

Functions: 90% of mineralocorticoid activity is carried out by aldosterone.

Aldosterone is very essential for life and it maintains the osmolarity and
volume of ECF. It is usually called life-saving hormone because, its absence
causes death within 3 days to 2 weeks. Aldosterone has three important
functions. It increases:

1. Reabsorption of sodium from renal tubules

2. Excretion of potassium through renal tubules
3. Secretion of hydrogen into renal tubules (thus maintaining acid-base
balance)

The effect of hypersecretion of aldosterone on sodium reabsorption is not

burdensome as the effect of hyposecretion, this shows how important it is
needed. Reabsorption of sodium by aldosterone invariably increases ECF as
water is always reabsorbed along with sodium. Increase in ECF and blood
volume would invariably lead to an increase in blood pressure.
Aldosterone-induced high blood pressure decreases the ECF volume
through two types of reactions (hemeostastic mechanism of the body to
restore balance which is called aldosterone escape phenomenon): the high
blood pressure

i. Stimulates secretion of atrial natriuretic peptide (ANP), brain

natriuretic peptide (BNP) and C-type natriuretic peptide (CNP)
muscles of the heart which causes excretion of sodium in spite of
increase in aldosterone secretion.
ii. causes pressure diuresis (excretion of excess salt and water by high
blood pressure) through urine. This decreases the salt and water
content in ECF, in spite of hypersecretion of aldosterone.
 Aldosterone sodium retaining effect is also evident in sweat gland, salivary
gland and the intestine as it prevents the secretion of sodium in sweat and
siliva as well as increase the absorption of sodium in the intestine.

Regulation: aldosterone secretion is regulated by four factors namely

potassium ion level in ECF, sodium ion in ECF, ECF volume and ACTH.

Stimulants are increased potassium ion in the ECF (the most effective),
decreased sodium ion in ECF, decreased ECF volume and ACTH while the
inhibitants are the reverse. Decrease in ECF sodium ion and ECF volume
uses renin-angiostensin system mechanism to restore balance.

2. Glucocorticoid: Glucocorticoids are secreted mainly by zona fasciculata of

adrenal cortex while a small quantity of glucocorticoids is also secreted by
zona reticularis and they are transported by a special plasma protein known
as glucocorticoids-binding globulin or transcortin. Ninety four percent of
glucocorticoids are transported by this protein, whereas about 6% of them
are found free in plasma. Albumin plays a very little role in glucocorticoid
transport. Glucocorticoids act mainly on glucose metabolism. They are:
i. Cortisol
ii. Corticosterone
iii. Cortisone.

Half-life of cortisol is 70 to 90 minutes and that of corticosterone is 50

minutes. Half-life of cortisone is not known.

Functions: Cortisol or hydrocortisone is more potent and it has 95% of

glucocorticoid activity. Corticosterone is less potent showing only 4% of
glucocorticoid activity. Cortisone with 1% activity is secreted in minute
quantity. There appears to be no cell within the body that does not have
receptors for the glucocorticoid hormones. The glucocorticoid hormones
have several effects:

i. They influence the metabolism of most body cells

ii. They increase the use of fats and excess amino acids for energy
production and reduce the use of glucose, this is called glucose
 sparing effect (anti-insulin action of glucocorticoids) so as to make
glucose available for use by the brain which does not use any other
energy source.
iii. They promote glycogen storage in the liver
iv. During fasting they stimulate the generation of glucose
v. They increase blood glucose levels by gluconeogenesis in liver
vi. They are involved in providing resistance to stressors
vii. They potentiate the lipolytic, vasoconstrictor and bronchiodilator
effect of catecholamines (adrenaline and noradrenaline).
viii. They potentiate calorigenic effect oif glucagon
ix. They decrease the permeability of vascular endothelium
x. They promote the repair of damaged tissues by promoting the
breakdown of stored protein to create amino acids
xi. They suppress the immune system
xii. They suppress inflammatory processes (Immunological reactions,
which are common during organ transplantation, may cause
rejection of the transplanted tissues. Glucocorticoids are used to
suppress the immunological reactions because of their
immunosuppressive action).
xiii. They maintain water balance by excretion of water
xiv. They stimulate the bone resorption (osteoclastic activity) and inhibit
bone formation and mineralization (osteoblastic activity).
xv. They increase catabolism of protein.

Regulation: Anterior pituitary controls the activities of adrenal cortex by

secreting ACTH. ACTH is mainly concerned with the regulation of cortisol
secretion and it plays only a minor role in the regulation of
mineralocorticoid secretion.

ACTH secretion is regulated by hypothalamus through corticotropin-

releasing factor (CRF).

CRF stimulates the corticotropes of anterior pituitary and causes the

synthesis and release of ACTH. CRF secretion is induced by several factors
 such as emotion, stress, trauma and circadian rhythm. CRF in turn, causes
release of ACTH, which induces glucocorticoid secretion.

Cortisol regulates its own secretion through negative feedback control by

inhibiting the release of CRF from hypothalamus and ACTH from anterior
pituitary although this negative feedback mechanism can be overridden by
hemorrhage and other related factors.

The rate of secretion of both ACTH and CRF is high in the morning and low
in the evening. Hypothalamus plays an important role in the circadian
fluctuations of ACTH secretion.

3. Adrenal sex hormones: They are secreted mainly by the zona reticularis
while smaller quantities are secreted by zona fasciculata. These are mainly
the male sex hormones, which are called androgens and a small quantity of
oestrogen and progesterone. The androgens are;
i. Dehydroepiandrosterone
ii. Androstenedione
iii. Testosterone
 Function: Dehydroepiandrosterone is the most active adrenal androgen.
Androgens, in general, are responsible for masculine features of the body.
But in normal conditions, the adrenal androgens have insignificant
physiological effects, because of the low amount of secretion both in males
and females

EXOGENOUS STERIODS

These are commercially available synthetic drugs or extracts with corticosteroid

effects. They either used as replacement of natural hormones (replacement
therapy) in patients with deficiency disorders such as Addison disease or to treat
a variety of other conditions such as arthritis, allergic conditions, asthma, skin
disorders, etc

Synthetic steroids that are commonly used are:

1. Cortisone and hydrocortisone, which are used for replacement therapy

have both glucocorticoid and mineralocorticoid effects
 2. Prednisolone has more glucocorticoid activity than mineralocorticoid
activity
3. Fludrocortisone (9-fluorocortisol) has more mineralocorticoid activity than
glucocorticoid activity. It has most potent mineralocorticoid effect.
4. Dexamethasone has only glucocorticoid effect.

APPLIED PHYDIOLOGY

Hypersecretion of adrenocortical hormones leads to the following conditions:

1. Cushing syndrome.
2. Hyperaldosteronism.
3. Adrenogenital syndrome.

1. Cushing syndrome: it is characterized by obesity.

Causes: It may be either due to pituitary origin (tumor in thebanterior
pituitary basophilic cells called cushing disease) or adrenal origin (tumor in
the tissues of the adrenal gland called cushing syndrome).
Signs and symptoms: (moon face, buffalo hump, pot belly, facial redness,
bone resoption and osteoporosis,hyperglycemia, hypertension,weakening
of muscles, thinning of extremities and skin etc
2. Hyperaldosteronism: increased secretion of aldosterone.
Causes: when it caused by a tumor in the zona glomerulosa of the adrenal
cortex, it is called primary hyperaldosteronism or conn’s syndrome.
Hyperaldosteronism due to other causes is called secondary
hperaldosteronism and these causes incluse congestive heart failure,
nephrosis, cirrhosis of liver and toxemia of pregnancy.
Signs and symptoms: increased ECF and blood volume, hypertension,
severe depletion of potassium, muscle weakness , metabolic alkalosis,
tetany etc.
3. Adrenogenital syndrome: secretion of abnormal quantities of adrenal
androgens develops adrenogenital syndrome. Testosterone is responsible
for the androgenic activity in adrenogenital syndrome.
 Causes: tumor of zona reticularis in adrenal cortex
Symptoms: in females, there is increased development of male sexual
characteristics, this is called adrenal virilism. Symptoms include
masculinization due to increased muscular growth, deepening of voice,
amenorrhea, enlargement of clitoris and male type of hair growth.
In males, sometimes, the tumor of estrogen secreting cells produces more
than normal quantity of estrogens which would lead to symptoms like
feminization, gynecomastia (enlargement of breast), atrophy of testis, loss
of interest in women.

Hyposecretion of adrenocortical hormones leads to the following conditions:

1. Addison’s disease or chronic adrenal insufficiency.

2. Congenital adrenal hyperplasia.

1. Addison’s disease:
Causes: Atrophy of adrenal cortex due to autoimmune diseases,
destruction of the gland because of tuberculosis, destruction of hormone-
secreting cells in adrenal cortex by malignant tissues, congenital failure to
secrete cortisol or adrenalectomy and failure to take hormone therapy.
Signs and symptoms: muscular weakness, dehydration, hypotension,
hypoglycemia, nausea, diarrhea, inability to withstand any form of stress
etc
2. Congenital adrenal hyperplasia READ IT UP.

ADRENAL MEDULLA

Microscopic anatomy: The adrenal medulla is mostly a modified, densely

innervated, sympathetic ganglion made made up of interlacing cords of cells
known as chromaffin cells. Chromaffin cells are also called pheochrome cells or
chromophil cells. These cells contain fine granules which are stained brown by
potassium dichromate. Adrenal medulla is formed by two types of chromaffin
cells:

1. Adrenaline-secreting cells (90%).

2. Noradrenaline-secreting cells (10%).

Hormones/secretions of the adrenal medulla: Adrenal medullary hormones are

the amines derived from catechol and so these hormones are called
catecholamines. They have a half-life of about 2minutes. Catecholamines secreted
by adrenal medulla are;

1. Adrenaline or epinephrine

2. Noradrenaline or norepinephrine

3. Dopamine

1. Catecholamines are synthesized from the amino acid tyrosine in the

chromaffin cells of adrenal medulla. These hormones are formed from
phenylalanine also. But phenylalanine has to be converted into tyrosine. The
processes involved in the synthesis of cathecholamine are shown in the diagram
below:
DOPA = Dihydroxyphenylalanine, PNMT = Phenylethanolamine-N-methyl
transferase.

Eighty five percent of noradrenaline is taken up by the sympathetic adrenergic

neurons. Remaining 15% of noradrenaline and adrenaline are degraded. The
diagram below shows the metolic process of cathecholamines.
Functions: Adrenaline and noradrenaline stimulate the nervous system.
Adrenaline has significant effects on metabolic functions and both adrenaline and
noradrenaline have significant effects on cardiovascular system.

Circulating adrenaline and noradrenaline have similar effect of sympathetic

stimulation. But, the effect of adrenal hormones is prolonged 10 times more than
that of sympathetic stimulation. It is because of the slow inactivation, slow
degradation and slow removal of these hormones. Effects of adrenaline and
noradrenaline on various target organs depend upon the type of receptors
present in the cells of the organs.

Noradrenaline causes vasoconstriction in skin, viscera, and skeletal muscles while

adrenaline increases heart rate and force of contraction, dilates bronchioles,
decreases peristalsis, increases conversion of glycogen to glucose in the liver,
causes vasodilation in skeletal muscles, causes vasoconstriction in skin and
viscera, increases use of fats for energy and increases the rate of cell respiration.
Regulation: cathecholamines are stimulated by sympathetic impulses from the
hypothalamus, and their functions duplicate and prolong those of the
sympathetic division of the autonomic nervous system (mimetic means “to
mimic”).

DOPAMINE

Dopamine is secreted by adrenal medulla. Type of cells secreting this hormone is

not known. Dopamine is also secreted by dopaminergic neurons in some areas of
brain, particularly basal ganglia. In brain, this hormone acts as a neurotransmitter.
Injected dopamine produces the following effects:

1. Vasoconstriction by releasing norepinephrine

2. Vasodilatation in mesentery

3.Increase in heart rate via beta receptors

4. Increase in systolic blood pressure.

Dopamine does not affect diastolic blood pressure. Deficiency of dopamine in

basal ganglia produces nervous disorder called parkinsonism

APPLIED PHYSIOLOGY

Pheochromocytoma: This condition is characterized by hypersecretion of

catecholamines.
Causes: caused by tumor of chromophil cells in adrenal medulla or rarely by a
tumor of sympathetic ganglia (extra-adrenal pheochromocytoma).

Signs and symptoms: hypertension referred to as endocrine hypertension,

anxiety, chest pain, fever, headache, hyperglycemia, metabolic disorders, nausea
and vomiting, palpitation, polyuria and glucosuria, sweating and flushing,
tachycardia, weight loss etc.

OTHER HORMONE PRODUCING STRUCTURES

Some other organs/glands of the body perform endocrine function. These include
the ovaries( oestrogen, progesterone), testis (testosterone etc),pineal gland
(melatonin), thymus;skin (cholecalciferol), kidneys
(erythropoietin,thrombopoietin & renin), heart (ANP etc), placenta
(oestrogen,progesterone), skin, adipose tissue (leptin, resistin), GIT (gastrin,
secretin etc) etc. These structures possess cell clusters that produce these
hormones and most times are not recognized as part of the endocrine system
because of the other roles they play in the body.

THE OVARIES

The ovaries are a pair of oval structures about 1.5 inches (4 cm) long.

Location: On either side of the uterus in the pelvic cavity.

Structure: each ovary has several hundred thousand primary follicles, which are
present at birth. During a woman’s childbearing years, only 300-400 400 of these
follicles will produce mature ova. As with sperm production in men, the supply of
potential gametes far exceeds what is actually needed, but this helps ensure the
continuation of the human species. Each primary ovarian follicle contains an
oocyte, a potential ovum or egg cell. Surrounding the oocyte are the follicle cells,
which secrete estrogen. Under the influence of LH, ruptured follicles (follicles that
have released their mature ovum) become the corpus luteum(within the ovary)
and begins to secrete progesterone as well as estrogen. Hormones produced in
smaller amounts by the corpus luteum are inhibin (a protein) and relaxin.

Hormones/secreions of the ovary: these are oestrogen (steroid), progesterone

(steroid), inhibin (protein) and relaxin (protein).

Functions of these hormones

1. Oestrogen
i. Promotes the maturation of the ovum in the ovarian follicle
ii. Stimulates the growth of blood vessels in the endometrium
(lining) of the uterus in preparation for a possible fertilized
egg.
iii. Stimulates development of secondary sex characteristics such
as growth of the duct system of the mammary glands, growth
of the uterus, and the deposition of fat subcutaneously in the
hips and thighs, closure of the epiphyseal discs in long bones,
and growth in height stops.
iv. Estrogen is also believed to lower blood levels of cholesterol
and triglycerides. For women before the age of menopause
this is beneficial in that it decreases the risk of atherosclerosis
and coronary artery disease.
v. In the brain, testosterone from the testes or the adrenal cortex
can be converted to estrogen, which may be important for
memory, especially for older people. Estrogen seems to have
non-reproductive functions in both men and women.
2. Progesterone
• It promotes the storage of glycogen and the further
growth of blood vessels in the endometrium, which thus
becomes a potential placenta.
• Stimulates the development of the secretory cells of the
mammary glands
3. Inhibin
 • It is secreted by the granulosa cells in the ovaries of women that acts
primarily to inhibit the secretion of follicle-stimulating hormone by
the anterior pituitary gland, indirectly inhibiting the secretion of
other hormones of the ovaries.

THE TESTES

There are two testes in humans. Each testis is about 1.5 inches long by 1 inch
wide (4 cm by 2.5 cm) and is divided internally into lobes.

Location: they are located in the scrotum, a sac of skin between the upper thighs

Structure: Each lobe contains several seminiferous tubules, in which

spermatogenesis takes place. These seminiferous tubules contain sustentacular
(Sertoli) cells which produce the hormone inhibin when stimulated by
testosterone. In between the loops of the seminiferous tubules are interstitial
cells which produce testosterone when stimulated by luteinizing hormone (LH)
from the anterior pituitary gland.

Hormones/secretions of the testes: these are testosterone (steroid) and inhibin

(protein).

Functions of these hormones

1. Testosterone
i. It promotes maturation of sperm in the seminiferous tubules
of the testes; this process begins at puberty and continues
throughout life.
ii. At puberty, it stimulates development of the male secondary
sex characteristics such as growth of all the reproductive
organs, growth of facial and body hair, growth of the larynx
and deepening of the voice, and growth (protein synthesis) of
the skeletal muscles and also the closure of the epiphyses of
the long bones.
 2. Inhibin
The function of inhibin is to decrease the secretion of FSH by the anterior
pituitary gland. The interaction of inhibin, testosterone, and the anterior
pituitary hormones maintains spermatogenesis at a constant rate.

Regulation: testosterone secretion is stimulated by leutinizing hormone (LH),

while inhibin secretion is stimulated by testosterone.

THE PINEAL GLAND

The pineal gland also called the epiphysis is a small con-shaped structure with a
length of about 10mm. it is reddish brown in color and is surrounded by a capsule.

Location: it is located at the back of the third ventricle which is a cavity within the
diencephalon area of the brain above the hypothalamus.

Structure: The pineal gland is connected to it by a short stalk containing nerves,

many of which terminate in the hypothalamus. It has two types of cells:

1. Large epithelial cells called parenchymal cells

2. Neuroglial cells.

In adults, the pineal gland is calcified. But, the epithelial cells exist and secrete the
hormonal substance.

Hormones/secretion: melatonin.

Function of melatonin

• In other mammals (not humans), it helps regulate seasonal

reproductive cycles.
• It stimulates the onset of sleep and increases its duration.
• It inhibits the onset of puberty by inhibiting the gonads.

Regulation: The secretion of melatonin is greatest during darkness and decreases

when light enters the eye and the retina signals the hypothalamus. A recent
discovery is that the retina also produces melatonin, which seems to indicate that
the eyes and pineal gland work with the biological clock (circadian rhythm) of the
hypothalamus.

THE THYMUS AS AN ENDOCRINE GLAND

Thymus has lymphoid function and endocrine function. It plays an important role
in development of immunity in the body. It weighs about 10 to 15 g at birth and
grows until the individual reaches puberty, when it begins to atrophy. Its
maximum weight, at puberty, is between 30 and 40 g and by middle age it has
returned to approximately its weight at birth.

Location: The thymus gland lies in front of the trachea below the thyroid gland
(upper part of the media-sternum and extends upwards into the root of the neck).

Structure: The thymus consists of two lobes joined by areolar tissue. The lobes
are enclosed by a fibrous capsule which dips into their substance, dividing them
into lobules that consist of an irregular branching framework of epithelial cells
and lymphocytes.

Hormones/secretions of the thymus: Thymus secretes two hormones namely

thymosin and thymin.

Functions:

• Thymosin is a peptide that accelerates lymphopoiesis and proliferation of T

lymphocytes.
• Thymin is also called thymopoietin. It suppresses the neuromuscular
activity by inhibiting acetylcholine release. Hyperactivity of thymus causes
myasthenia gravis
THE KIDNEY AS AN ENDOCRINE ORGAN

The kidney’s anatomical dimension have been previously explained to you,

students under the urinary system and such only its endocrine function will be
related here.

The Kidneys secrete five hormonal substances:

1. Erythropoietin

2. Thrombopoietin

3. Renin

4. 1,25-dihydroxycholecalciferol (calcitriol)

5. Prostaglandins

• Erythropoietin
Erythropoietin is a glycoprotein with 165 amino acids. It is secreted by
endothelial cells of peritubular capillaries in the kidney(functional
anatomy). It stimulates the bone marrow and causes erythropoiesis
(function) . The stimulant for its secretion is hypoxia (regulation).
• Thrombopoietin
Thrombopoietin is a glycoprotein. It is secreted by kidneys and liver. It
stimulates the production of platelets.
• Renin
The granular cells of juxtaglomerular apparatus of the kidney secrete renin
(functional anatomy). It acts on a specific plasma protein called alpha-2
globulin which is also called angiotensinogen or renin substrate. Renin
converts angiotensinogen into angiotensin I, which is converted into
angiotensin II by a converting enzyme.
• 1,25-dihydroxycholecalciferol (calcitriol)
25-hydroxycholecalciferol from the liver is activated into 1,25-
dihydroxycholecalciferol by parathormone in kidney. The activated vitamin
D plays an important role in the maintenance of blood calcium level. It acts
 on the intestinal epithelium and enhances absorption of calcium from
intestine into the blood.
• Prostaglandins
Prostaglandins secreted from kidney are PGA2 and PGE2 . These hormones
are secreted by juxtaglomerular cells and type I interstitial cells present in
medulla of kidney. They decrease the blood pressure by systemic
vasodilatation, diuresis and natriuresis.

THE HEART AS AN ENDOCRINE ORGAN

The hormones secreted by the heart are atrial natriuretic peptide (ANP), brain
natriuretic peptide (BNP) and C-type natriuretic peptide

• Atrial natriuretic peptide (ANP)

ANP is a polypeptide with 28 amino acids. It is secreted by atrial
musculature of the heart. It can also be found in the hypothalamus of the
brain. ANP is secreted during overstretching of atrial muscles in conditions
like increase in blood volume which in turn leads to the excretion of
sodium (and water) through urine.
Functions: Its major functions are to maintain extracellular fluid (ECF)
volume and blood volume and also lower blood pressure. It maintains
ECF/blood volume and excreting sodium in the following ways
i. Increasing glomerular filtration rate by relaxing mesangeal cells and
dilating afferent arterioles
ii. Inhibiting sodium reabsorption from distal convoluted tubules and
collecting ducts in kidneys
iii. Increasing the secretion of sodium into the renal tubules.

It decreases blood pressure in the following ways

i. Vasodilatation by relaxing the smooth muscle fibers, mainly in arterioles
and venules
ii. Inhibiting renin secretion from juxtaglomerular appara tus of kidney
iii. Inhibiting vasoconstrictor effect of angiotensin II
 iv. Inhibiting vasoconstrictor effects of catecholamine (adrenaline and
noradrenaline).

• Brain natriuretic peptide (BNP)

Brain natriuretic peptide (BNP) is also called B-type natriuretic peptide. It is
a polypeptide with 32 amino acids. It is secreted by the cardiac muscle. It is
also secreted in some parts of the brain. BNP has same actions of ANP.
More research are needed for complete understanding of the role,
regulation of this hormone secretion.
• C-type natriuretic peptide
C-type natriuretic peptide (CNP) is the newly discovered peptide hormone.
It is a 22 amino acid peptide. Initially, it was identified in brain. Now, it is
known to be secreted by several tissues which include myocardium,
endothelium of blood vessels, gastrointestinal tract and kidneys. It is
believed that it has similar action of atrial natriuretic peptide.
LOCAL HORMONES

Local hormones are the substances which act on the same area of their secretion
or in immediate neighborhood. The endocrine hormones are secreted in one
place but execute their actions on some other remote place.

Local hormones are usually released in an inactive form and are activated by
some conditions or substances.

Local hormones are classified into two types:

I. Hormones synthesized in tissues

II. II. Hormones synthesized in blood.

Local hormones synthesized in the tissues are:

• Prostaglandins and related substances

• Other local hormones synthesized in tissues

1. Prostaglandins and related substances: these are

• Prostaglandins
• Thromboxanes
• Prostacyclin
• Leukotrienes
• Lipoxins

2.Other local hormones synthesized in tissues include

• Acetylcholine
• Serotonin
• Histamine
• Substance P
• Heparin
• Leptin
• Gastrointestinal hormones e.g gastrin
Local hormones synthesized in blood

These are

• Serotonin
• Angiotensinogen
• Kinins e.g bradykinin and kallidin

Assignment

Read up the functions/actions of these local hormones.

GLOSSARY

Amino acid Chemical: compound that is the basic building block of proteins and
enzymes.

Carbohydrate: A group of compounds (including starches and sugars) that are a

major food source.

Catecholamines: A collective term for adrenaline, noradrenaline and dopamine.

Cortex: The outermost layer of an organ.

Corticosteroids: Steroid hormones released by the adrenal cortex, further

divided into glucocorticoids and mineralocorticoids.

Cortisol: The major glucocorticoid steroid released by the adrenal gland.

Cytoplasm: The part of the cell enclosed within the cell membrane.

Downregulation: The reduction in the number of hormone receptors of a cell,

often the response of a cell to prolonged periods of high circulating levels of a
hormone.

Electrolytes: A group of chemical elements or compounds that includes sodium,

potassium, calcium, chloride and bicarbonate.

Fatty acids: Dietary fats that have broken down into elements that can be
absorbed into the blood.

Free T4: Thyroxine in the blood that is not bound to proteins.

Ganglion: A mass, or group, of nerve cells.

Gland: Any organ in the body that secretes substances not related to its own,
internal, functioning.

Glucocorticoids: A group of hormones that exert their major effect on the

metabolism of carbohydrates.

Gluconeogenesis: Creation of new glucose from non‐carbohydrate substrates.

Glycogen: A carbohydrate (complex sugar) made from glucose.

Glycogenolysis: Breakdown of glycogen to create glucose.

Hormonal stimulation: Stimulation of a gland that produces a change in the

activity of that gland in response to hormones released by other organs.

Hormone: Chemical substance that is released into the blood by the endocrine
system, and has a physiological control over the function of cells or organs other
than those that created it.

Humoral stimulation: Stimulation of a gland that produces a change in the

activity of that gland in response to changing levels of certain ions and nutrients
in the blood.

Hyperglycaemia: High blood levels of glucose.

Hypoglycaemia: Low blood levels of glucose.

Hypovolaemia: Low levels of fluid in the circulation.

Ion: An atom or group of atoms that carry an electrical charge.

Lipids: A group of organic compounds, including the fats, oils, waxes, sterols and
triglycerides.

Medulla: The most internal part of an organ.

Mineralocorticoids: A group of hormones released by the adrenal glands that

exert their effect on the electrolytes and water balance in the body.

Neural stimulation: Stimulation of a gland that produces a change in the activity

of that gland in response to direct nervous activity.

Osmotic: The movement of water through a semi permeable barrier from an area
of low concentration of a chemical to an area of high concentration of a chemical.

Osteoclasts: A type of cell that breaks down bone tissue and thus releases the
calcium used to create bones.
Substrate: A molecule on which an enzyme acts.

Triglycerides: A form of fatty acid having three fatty acid components.

Upregulation: The increase of hormone receptors of a cell, usually in response to

low circulating levels of a hormone.