Pituitary gland

Anatomy of pituitary gland

Called Hypophysis
0.5 to 1g in wt
Situated in a pocket of the sphenoid bone at
the base of the brain called sella turcica.
Diaphragma sellae – deflection of
durameter that closes the cavity
Has 2 portions- adenohypophysis and
neurohypophysis
 Embroyology
Anterior pituitary develops from Rathkes
pouch which is a upward outpouching of
roof of oral cavity
Posterior pituitary develops from
downward outpouching from brain in
the floor of 3rd ventricle
Blood supply
Posterior pituitary – supplied mainly by
inferior hypophyseal artery  capillary
plexus  dural sinus
Anterior pituitary – supplied by superior
hypophyseal artery which forms two
plexuses
Primary plexus –lies in median eminence
Secondary plexus – lies in anterior pituitary
gland
Neurohypophysis
Neurovascular structure
Parts – Pars nervosa
Infundibulum
Median eminence
Contains axonal processes, glial like cells called
pituicytes along with fenestrated capillaries
Hormones released –
1.Antidiuretic hormone(vasopressin)
2.Oxytocin
Cell bodies of axonal processes are located
in supraoptic nuclei and paraventricular
nuclei of hypothalamus

Cell bodies are magnocellular that project

axons as hypothalamohypophysial tracts
 Adenohypophysis
Anterior portion of the gland
Parts – 1. Pars tuberalis
2. Pars distalis
3. Pars intermedia
Made of interlacing cell cords and
fenestrated sinusoidal capillaries
Has 5 types of cells that secrete 6
hormones collectively called anterior
pituitary hormones
Cell types of anterior pituitary
• Growth
Somatotropes
hormone

• Prolactin
Lactotropes
 • Adrenocorticotropic
Corticotropes
hormone

• Thyroid stimulating
Thyrotropes hormone

• Follicle stimulating hormone

Gonadotropes • Luteinizing hormone
Hypothalamo pituitary axes (endocrine axes)
Each endocrine axis is composed of three
levels of endocrine cells:
1. Hypothalamic neurons,
2. Anterior pituitary cells, and
3. Peripheral endocrine glands.
First level – hypothalamic neurons
Hypophysiotropic region in hypothalamus(parvicellular)

Project axons to median eminence

Release releasing or inhibitory hormones at median

eminence

They enter primary plexus and carried by long portal veins to

secondary plexus in ant pituitary

They diffuse out and stimulate or inhibit specific cell type in

ant pituitary
 Hypothalamic hormones
1. Corticotropin releasing hormone – corticotropes
2. Thyrotropin releasing hormone – thyrotropes
3. Gonadotropin releasing hormone – gonadotropes
4. Growth hormone releasing hormone – stimulatory
to somatotropes
5. Growth hormone inhibitory
hormone( Somatostatin) – inhibitory to
somatotropes
6. Dopamine – inhibitory to lactotropes
7. ? Prolactin releasing factor – stimulatory to
lactotropes
Second level – ant pituitary hormones
Hormone Target gland
Adrenocorticotropic Adrenal cortex
hormone
Thyroid stimulating Thyroid gland
hormone
Follicle stimulating Ovary and testis
hormone
Luteinizing hormone Ovary and testis

Growth hormone Liver

Prolactin No target gland
The lactotrope differs from the other endocrine cell
types of the adenohypophysis in two major ways:

The lactotrope is not part of an endocrine axis.

This means that PRL acts directly on
nonendocrine cells (primarily of the breast) to
induce physiological changes.

Production and secretion of PRL are

predominantly under inhibitory control by the
hypothalamus.
Third level – peripheral endocrine glands
Hormone Target gland Hormones

Adrenocorticotropic Adrenal cortex Cortisol, aldosterone

hormone
Thyroid stimulating Thyroid gland Triodo
hormone thyronine,tetraiodothyron
ine
Follicle stimulating Ovary and testis Estrogen, progesterone,
hormone testosterone and inhibin
Luteinizing hormone Ovary and testis

Growth hormone Liver Insulin like growth factor

( IGF 1 & IGF 2 )
Prolactin No target gland NONE
 Hypothalamic-pituitary-adrenal (HPA)
axis Hypothalamic
CRH neuron

Primary plexus
LONG LOOP

SHORT LOOP

Corticotrope
Secondary
plexus
ACTH

ADRENAL
 Hypothalamic-pituitary-testis and
hypothalamic pituitary ovary axis
Hypothalamic
GNRH neuron

Primary plexus
LONG LOOP

SHORT LOOP

Gonadotrope
Secondary
plexus
FSH AND LH

TESTIS OR
OVARY
 Hypothalamic-pituitary-thyroid axis
Hypothalamic
TRH neuron

Primary plexus
LONG LOOP

SHORT LOOP

Thyrotrope
Secondary
plexus
TSH

Thyroid
 Hypothalamic-pituitary-liver axis
Hypothalamic
GHRH neuron

Primary plexus
LONG LOOP

SHORT LOOP

Somatotrope
Secondary
plexus
GH

IGF LIVER
Features of endocrine axes
1. The activity of a specific axis is normally maintained
at a set point
2. Hypothalamic hypophysiotropic neurons are often
secreted in a pulsatile manner
3. Abnormally low or high levels of a peripheral
hormone (e.g., thyroid hormone) may be due to a
defect at the level of the peripheral endocrine gland
(e.g., thyroid), the pituitary gland, or the
hypothalamus. Such lesions are referred to as
primary, secondary, and tertiary endocrine
disorders, respectively
 Summary
Anterior pituitary lobe Posterior pituitary lobe
Epithelial tissue Neural tissue
Has neurovascular connection Has neural connection with
with hypothalamus hypothalamus
Hormones synthesized by Hormones are synthesized in
specific cell types in gland itself hypothalamic neurons &
transported to gland
Part of endocrine axes -
Hypothalamic releasing or -
inhibitory hormones control
secretion of ant pit hormones
Anterior pit hormones
Hypothalamic hormone Cell type Ant pit hormone

CRH CORTICOTROPE ACTH

TRH THYROTROPE TSH

GNRH GONADOTROPE FSH, LH

GHRH SOMATOTROPE GH

SOMATOSTATIN SOMATOTROPE INHIBIT GH RELEASE

DOPAMINE LACTOTROPE INHIBIT PRL RELEASE

PRF LACTOTROPE PRL

Anterior pituitary hormones
Feedback
control of
growth
hormone
Regulation of Growth Hormone
Secretion
GH secretion controlled primarily by hypothalamic
GHRH stimulation and somatostatin inhibition
Neurotransmitters involved in control of GH
secretion– via regulation of GHRH and somatostatin
Regulation of Growth Hormone
Secretion
Neurotransmitter systems that stimulate GHRH
and/or inhibit somatostatin
Catecholamines acting via a2-adrenergic receptors
Dopamine acting via D1 or D2 receptors
Excitatory amino acids acting via both NMDA and non-
NMDA receptors
Regulation of Growth Hormone
Secretion
 b-adrenergic receptors stimulate somatostatin release
and inhibit GH
 b-adrenergic receptors inhibit hypothalamic release of
GHRH
Growth hormone vs. metabolic state

When protein and energy intake are adequate, it is

appropriate to convert amino acids to protein and stimulate
growth. hence GH and insulin promote anabolic reactions
during protein intake
During carbohydrate intake, GH antagonizes insulin
effects-- blocks glucose uptake to prevent hypoglycemia. (if
there is too much insulin, all the glucose would be taken
up).
When there is adequate glucose as during absorptive
phase, and glucose uptake is required, then GH secretion is
inhibited so it won't counter act insulin action.
Growth hormone vs.
metabolic state
During fasting, GH antagonizes insulin action and helps
mediate glucose sparing, ie stimulates gluconeogenesis
In general, during anabolic or absorptive phase, GH
facilitates insulin action, to promote growth.
during fasting or post-absorptive phase, GH opposes
insulin action, to promote catabolism or glucose sparing
Growth
hormone
and
metabolic
state
Clinical assessment of GH
Random serum samples not useful due to
pulsatile pattern of release
Provocative tests necessary
GH measurement after 90 min exercise
GH measurement immediately after onset of sleep
Definitive tests
GH measurement after insulin-induced hypoglycemia
Glucose suppresses GH levels 30-90 min after
administration– patients with GH excess do not
suppress
Measurement of IGF-1 to assess GH excess
Acromegaly and Gigantism
Caused by eosinophilic adenomas of
somatotrophs
Excess GH leads to development of gigantism if
hypersecretion is present during early life– a
rare condition
Symmetrical enlargement of body resulting in true
giant with overgrowth of long bones, connective
tissue and visceral organs.
Excess GH leads to acromegaly if
hypersecretion occurs after body growth has
stopped.
Elongation of long bones not possible so there is
over growth of cancellous bones– protruding jaw,
thickening of phalanges, and over growth of visceral
organs
Acromegaly
Acromegaly
A) before presentation;

B) at admission
Harvey Cushing’s first
reported case
Gigantism

Identical twins, 22 years old, excess GH secretion

ACTH: adrenocorticotropic hormone:
synthesis and regulation of secretion
Produced in corticotrophs
ACTH is produced in the anterior pituitary by
proteolytic processing of Prepro-opiomelanocortin
(POMC).
Other neuropeptide products include b and g
lipotropin, b-endorphin, and a-melanocyte-
stimulating hormone (a-MSH).
ACTH is a key regulator of the stress response
ACTH synthesis

ACTH

Processing and cleavage of pro-opiomelanocortin (POMC)

ACTH
 ACTH is made up of 39 amino acids
 Regulates adrenal cortex and synthesis of
adrenocorticosteroids
 a-MSH resides in first 13 AA of ACTH
 a-MSH stimulates melanocytes and can darken skin
 Overproduction of ACTH may accompany increased
pigmentation due to a-MSH.
Melanocyte-stimulating hormone
(MSH)
MSH peptides derived by proteolytic cleavage of
POMC
a-MSH has antipyretic and anti-inflammatory
effects
Also inhibits CRH and LHRH secretion
Four MSH receptors identified
May inhibit feeding behavior
ACTH has MSH-like activity
However– MSH has NO ACTH like activity
Regulatio
n of ACTH
secretion
Regulation of ACTH secretion
Stimulation of release
CRH and ADH
Stress
Hypoglycemia
CRH and ADH both synthesized in hypothalamus
ADH (a.k.a. vasopressin) is released by posterior
pituitary and reaches anterior pituitary via inferior
hypophyseal artery.
ACTH
Circadian pattern of release
Highest levels of cortisol are in early AM following
ACTH release
Depends on sleep-wake cycle, jet-lag can result in
alteration of pattern
Opposes the circadian pattern of growth hormone
secretion
Regulation
of ACTH
ACTH
Acts on adrenal cortex
stimulates growth of cortex (trophic action)
Stimulates steroid hormone synthesis

Lack of negative feedback from cortisol results in

aberrantly high ACTH, elevated levels of other
adrenal corticosteroids– adrenal androgens
Adrenogenital syndrome: masculization of female
fetus
Glycoprotein hormones
 LH, FSH, TSH and hCG
 a and b subunits
 Each subunit encoded by different gene
a subunit is identical for all hormones
b subunit are unique and provide biological specificity
Glycoprotein hormones
Glycoprotein hormones contain two subunits, a common a
subunit and a distinct b subunit:
TSH, LH, FSH and hCG.
Gonadotrophs
Cells in anterior pituitary that produce LH and
FSH
Synthesis and secretion stimulated by GnRH–
major effect on LH
FSH secretion controlled by inhibin
Pulsitile secretion of GnRH and inhibin cause
distinct patterns of LH and FSH secretion
LH/FSH
Pulsatile pattern of secretion
LH pulses are biphasic (every 1 minute, then large pulse
at 1 hour)
FSH pulses are uniphasic
Diurnal– LH/FSH more pronounced during
puberty
Cyclic in females– ovarian cycle with LH surge at
time of ovulation
Males are not cyclic, but constant pulses of LH
cause pulses of testosterone to be produced
Pulsitile secretion of GnRH and LH
Regulation of LH/FSH
Negative feed-back
Inhibin produced by testes and ovaries Decreases FSH
b-subunit expression
Testosterone from Leydig cells– synthesis stimulated by
LH, feedsback to inhibit GnRH production from
hypothalamus and down-regulates GnRH receptors
Progesterone– suppresses ovulation, basis for oral
contraceptives. Works at both the level of pituitary and
hypothalamus.
Regulation of LH/FSH
Dopamine, endorphin, and prolactin inhibit
GnRH release.
Prolactin inhibition affords post-partum contraceptive
effect
Overproduction of prolactin via pituitary tumor
can cause amenorrhea– shuts off GnRH
Treated with bromocryptine (dopamine agonist)
Surgical removal of pituitary tumor
Regulation of LH/FSH
Positive feedback
Estradiol at high plasma concentrations in late follicular
phase of ovarian cycle stimulates GnRH and LH surge–
triggers ovulation
Regulation of
gonadotropin
secretion
Thyrotrophs
Site of TSH synthesis
Pattern of secretion is relatively steady
TSH secretion stimulated by TRH
Feedback control by T3 (thyroid hormone)
Feedback
control of
thyroid
function
Lacotrophs
Site of production of prolactin
Lactogenesis (milk synthesis) requires prolactin
Tonically inhibited
Of the anterior pituitary hormones, the only one
Multifactoral control, balance favors inhibition
Dopamine inhibits prolactin
Prolactin releasing hormone is TRH
Ocytocin also stimulates prolactin release
Estradiol enhances prolactin synthesis
Prolactin
Stimulates breast development and lactogenesis
May be involved in development of Leydig cells in pre-
pubertal males
Immunomodulatory effects– stimulates T cell
functions
Prolactin receptors in thymus
Clinical assessment of PRL
Single basal serum PRL measurement sufficient to
determine excess
PRL deficiency not a usual clinical concern
PRL is only anterior pituitary with predominant
negative control by hypothalamus– often elevated
by lesions that interfere with portal blood flow.
Elevated by primary PRL adenomas of pituitary
Posterior pituitary hormones:
ADH (AVP) and Oxytocin
(hypothalamic hormones)
Both are synthesized in the cell bodies of
hypothalamic neurons
ADH: supraoptic nucleus
Oxytocin: paraventricular nucleus
Both are synthesized as preprohormones and
processed into nonapeptides (nine amino acids).
They are released from the termini in response to
an action potential which travels from the axon
body in the hypothalamus
Structures of ADH and oxytocin
Oxytocin: stimulates myoepithelial
contractions
 In uterus during parturition
 In mammary gland during lactation
Oxytocin: milk ejection from
lactating mammary gland
 suckling is major stimulus for release.
 sensory receptors in nipple connect with nerve fibers
to the spine, then impulses are relayed through brain
to PVN where cholinergic synapses fire on oxytocin
neurons and stimulate release.
Oxytocin: uterine contractions
Reflexes originating in the cervical, vaginal and uterus
stimulate oxytocin synthesis and release via neural
input to hypothalamus
Increases in plasma at time of ovulation, parturition,
and coitus
Estrogen increases synthesis and lowers threshold for
release
POSTERIOR PIT HORMONES
OXYTOCIN
ADH ( VASOPRESSIN )