Fundação Universidade Federal do Rio Grande

Instituto de Ciências Biológicas-ICB

Prova de qualificação
Aula II

Estrutura e função do sistema

hipófise-hipotálamo

Micheli Castro
 Existem vários órgãos envolvidos na captação e transmissão de estímulos
e na elaboração de respostas…e o hipotálamo é o centro coletor de informações
relativas ao bem estar do corpo, que por sua vez, grande parte dessa informação é
usada para controlar as secreções de muitos hormônios hipofisários.

Receptores

Fibras nervosas sensitivas

transmitem os impulsos nervosos aos

Recebem os Produzem estímulos que
estímulos do nos dão a sensação de
exterior. fome, sede, …

Processam a resposta
adequada.
Centros nervosos

Planeta Terra — 9.º ano

 Hypothalamus
Regulates the activity of the nervous and
endocrine systems
Highest level of endocrine control
1)Secrets regulatory hormones that
control the anterior pituitary gland
2) Releases hormones at the posterior
pituitary gland
3) Exerts direct neural control over the
endocrine cells of the adrenal
medullae.
 Hypothalamus
• Located at the basal part of the diencephalon lying
below the thalamus
• Split into left & right halves by the 3rd ventricle
• Has many neuroendocrine, behavioural and
autonomic functions. Sexually dimorphic.
– Sexual and ingestive behaviours
– Control of body temperature
– Integration of the cardiovascular & hormonal responses to
stress
 Hypothalamus
• Within the hypothalamus there are many clusters of
neurons hypothalamic nuclei
– Supraoptic, paraventricular, arcuate, ventromedial &
suprachiasmatic
– Medial anterior hypothalamic & medial preoptic areas
• These have either direct neural or indirect vascular
connections to the pituitary gland
 *
*
*
#

#
Parvocellular &
Magnocellular
Neurosecretory
Neurons

Rostral Hyp
*
# Medial Basal Hyp
 Magnocellular System
• Magnocellular neurons are found in the supraoptic
nuclei & paraventricular nuclei
– Term “magno” means large
– Axons from these neurons project to the posterior lobe of
the pituitary
• Oxytocin and ADH (vasopressin) are synthesized in
the cell bodies of both nuclei.
– During synthesis, they associate with the neurophysin, a
binding protein
 Characteristics of hypothalamic
releasing hormones
• Secretion in pulses
• Act on specific membrane receptors
• Transduce signals via second messengers
• Stimulate release of stored pituitary hormones
• Stimulate synthesis of pituitary hormones
• Stimulates hyperplasia and hypertophy of target cells
• Regulates its own receptor
 Pituitary (Hypophysis)

• Pituitary gland – two-lobed organ that secretes nine

major hormones
• Neurohypophysis – posterior lobe (neural tissue)
and the infundibulum
– Receives, stores, and releases hormones from the
hypothalamus
• Adenohypophysis – anterior lobe, made up of
glandular tissue
– Synthesizes and secretes a number of hormones
Major Endocrine Organs: Pituitary (Hypophysis)
 Pituitary-Hypothalamic Relationships: Anterior
Lobe

• There is no direct neural contact with the

hypothalamus
• There is a vascular connection, the hypophyseal
portal system, consisting of:
– The primary capillary plexus
– The hypophyseal portal veins
– The secondary capillary plexus
 Pituitary gland
• Two parts of the pituitary are anatomically are
functionally DIFFERENT.
• Adenohypophysis (anterior)
– Derives from an inward invagination of the oral ectoderm
of the primitive mouth cavity known as Rathke’s pouch
• Neurohypophysis (posterior)
– Arises from the neural ectoderm of the floor of the
forebrain
 Anterior Lobe
• Contains a variety of cell types which secrete
hormones
 Posterior Lobe
• Contains no secretory cell bodies which
synthesize hormones
• Composed of terminals of axons that originate
in the hypothalamus
• Cell body of neuron secretes hormone which
travels down to the end of the axon
• Posterior pituitary is ALL neural
 Pituitary Hormones:
a. Anterior pituitary (adenohypophysis)
1. Luteinizing hormone (LH)
2. Follicle Stimulating Hormone (FSH)
3. Thyroid Stimulating Hormone (TSH)
4. Growth Hormone (Somatotropin; GH)
5. Adrenocorticotropic Hormone (ACTH)
6. Prolactin (Prl)
b. Posterior pituitary (neurohypophysis)
Oxytocin
Vasopressin (Antidiuretic Hormone; ADH)
c. Intermediate lobe
Melanocyte Stimulating Hormone (MSH)
 Anterior Pituitary Control
• Hypothalamic control of anterior pituitary is very
different than for the posterior pituitary
• AP is regulated by chemical factors or hormones
produced in the hypothalamus
• Each anterior pituitary hormone probably has dual
hypothalamic hormones - one inhibits and one
stimulates
• AP-regulating hormones travel from the
hypothalamus to the anterior lobe by a specialized
vascular route
Hypothalamic-pituitary portal system
• The specialized vascular route is termed the
hypothalamic-pituitary portal system
• Portal system = two beds of capillaries
connected by straight vessels
Figure 5.2.13 Feedback loops in a typical
hypothalamo-hypophyseal axis. The target cell
types (shaded area) may be any of those present
in the anterior pituitary.
They operate in a closed-loop feedback mode to
maintain relatively steady plasma levels of the
hormones concerned, subject to modifications of
the hypothalamic drive by inputs from outside
the body (exteroceptive signals), or intrinsic to
the brain (pulse-generator).
Long-loop and short-loop negative feedbacks
involve respectively, the peripheral hormones
and the tropic hormones.
Anterior pituitary hormones: Function
• ACTH and TSH stimulate other endocrine
gland
• ACTH regulates the function of the adrenal
cortex; increases release of adrenal steroids
• TSH regulates the function of the thyroid
gland; increases release of thyroid hormones
 Pituitary Hormone Actions:
• FSH (secreted by gonadotrope cells)
– ovaries, stimulates development of eggs and follicles
– testes, stimulates production of sperm
• LH (secreted by gonadotrope cells)
– females, stimulates ovulation and corpus luteum to
secrete progesterone and estrogen
– males, stimulates interstitial cells of testes to secrete
testosterone
– One hypothalamic factor (gonadotropin-releasing
hormone – GnRH - decapeptide) stimulates the
secretion of both hormones
Anterior pituitary hormones: Function
of prolactin
• Prolactin is the major hormone responsible for milk
production (lactogenesis) and also is part of the hormone
complex that promotes growth/development of the
mammary glands (mammogenesis).
• Blood levels of prolactin are low in non-pregnant, non-
lactating females and in males.
• However, during pregnancy and lactation, blood levels of
prolactin increase, consistent with the hormone's role in
mammary gland development and lactogenesis.
• Essentially a hormone of reproduction.
• Male,  LH sensitivity in testes, thus  testosterone secretion
(gonadotropic effect in males)
Control of prolactin
 Prolactin secretion regulation
• Stimuli which increase is :
• After2 to 3 hours of onset of sleep and continues through
out the sleep
• Exercise and stress
• Pregnancy
• Nursing and breast stimulation
• Primary hypothyroidism
• Dopamine antagonist like phenothiazine
• Stimuli which decrease is :
• Prolactin inhibitory factor (Dopamine)
• Dopamine agonists: bromocriptine.
 Maintenance of Lactation:
Galactopoiesis
• Hormonal control & milk removal
• Prolactin along with growth hormone,
glucocorticoids ,parathyroid hormone, and
Insulin .
 Prolactin (PRL): Disorders
Hyperprolactinemia
• Hypersecretion due to adenohypophyseal tumors; Common
type of pituitary tumour (accounts for 60% of pituitary
tumours). Other causes are due to primary hypothyroidism .
The effects are due to associated decreased in FSH and LH
levels
• Results in galactorrhea (inappropriate milk production), lack
of menses and infertility in women; impotence in men.
• Treatment: Dopamine agonist: Bromocriptine .
• Surgical removal of tumour .
Anterior pituitary hormones: Function
of Growth Hormone
• GH is important to growth and the control of
metabolic functions
• It acts directly on target cells which contain GH
receptors
• And as importantly, indirectly via the secondary
generation of growth factors (peptides) called
somatomedins in the liver.
• There are at least two somatomedins (A and C.
Somatomedins are also called insulin-like growth
factors (IGF-1 and -2)
Metabolic Action of GH
Control of GH secretion
 Growth Hormone Regulation
• Stimulation by:
• Growth hormone releasing hormone ,Hypoglycemia,
Decrease in blood free fatty
acids,Fasting,Exercise,Stress,Estrogens,Androgens,
deep sleep.
• Inhibition by:
• Somatostatin,Hyperglycemia,Rising free fatty
acids,somatomedins(IGF),GH,Cortisol,
• Pregnancy, REM sleep .
 Growth Hormone
• Abnormalities
– Dwarfism: decreased secretion of hormone (prolonged
steroid use) or decreased number of receptors (African
pigmies)
– Gigantism: excess secretion occurs during aldolescence
before epiphyseal plates close. up to 8’ tall, normal body
proportions
– Acromegaly: excess secretion occurs during adulthood
after epiphyseal plates close. Enlargement of extremities
(hands and feet) and face, thickening of soft tissue.
 Other Hormones Affecting Growth:
Thyroid Hormones:
enhance GH effects and IGF production
 tissue sensitivity to GH

Insulin/Glucagon:
regulate metabolism
Insulin:
aa uptake into muscle and protein synthesis in bone matrix formation;
GH/IGF receptors; IGF synthesis; vitamin D production
Gonadal Steroids: (cause epiphyseal closure)
Androgens - anabolic effects on muscle;  GH secretion
Estrogens - mechanism unclear
osteoporosis in E2 deficiency
 POSTERIOR PITUITARY
• Hormones (ADH, oxytocin) synthesized in
hypothalamus
• Travel down axons, stored in posterior pituitary
• Released in response to increase frequency of action
potentials in same axons
• Modified neurotransmitters
• Whole system is nervous – cell bodies of neuron are
in hypothalamus, axons terminate in posterior
pituitary.
 Actions of ADH: Water retention

• ADH (vasopressin) has two actions, one on the

kidney and the other on vascular smooth
muscle. These actions are mediated by
different receptors, different intracellular
mechanisms, and different second
messengers.
 ADH: Increase in water permeability.
• The major action of ADH is to increase the water permeability of cells in
the kidney distal tubule and collecting duct.
• The receptor for ADH on kidney cells is a V2 receptor, which is coupled to
adenylyl cyclase via a Gs protein.
• The second messenger is cAMP, which, via phosphorylation steps, directs
the insertion of water channels, aquaporin 2, into the kidney cell
membranes.
• The increased water permeability of the cells allows more water to be
reabsorbed by the collecting ducts (ie water moves from urine to blood)
and makes the urine MORE concentrated or hyperosmotic.
 ADH and contraction of vascular
smooth muscle
• The second action of ADH is to cause contraction of
vascular smooth muscle (as implied by its other
name, vasopressin).
• The receptor for ADH on vascular smooth muscle is a
V1 receptor, which is coupled to phospholipase C via
a G protein.
• The second messenger for this action is an IP2/Ca
cascade which produces contraction of vascular
smooth muscle, constriction of arterioles, and
increased total peripheral resistance.
Figure 5.2.10 Summary of the pathways
involved in control of ADH secretion.
Factor affecting ADH secretion
 ADH: Disorders
• Hyposecretion due to damage of
hypothalamic nucleus or neurohypophysis 
diabetes insipidus - excessive urine production
(polyuria) and thirst
• Hypersecretion  SIADH (syndrome of
inappropriate ADH secretion)
– water retention, cerebral edema, headache,
weight gain, hypo-osmolarity
 Diabetes Insipidus:
Central (lack of ADH secretion): Head injury or
tumour
Nephrogenic (renal tubule insensitivity to ADH)

Polyuria (excessive watery urine) followed by

polydypsia;  thirst
Treatment :Analogues of ADH:Desmopressin (Nasal
Spray)
Tumour: surgical removal of tumour
 Actions of Oxytocin: Milk letdown

• Milk ejection. Prolactin stimulates lactogenesis. The

milk is stored in mammary alveoli and small milk
ducts.
• The major action of oxytocin is to cause milk
letdown. When oxytocin is secreted in response to
suckling or to conditioned responses, it causes
contraction of myoepithelial cells lining these small
ducts, forcing the milk into large ducts. The milk
collects in cisterns and then flows out under pressure
through the teat
 Actions of Oxytocin: Uterine
contractions
• Oxytocin causes powerful rhythmic contractions of
primed uterine smooth muscle (myometrium).
• Oxytocin plays a role in parturition (the process of
birth).
• Oxytocin can be used clinically to assist the birth
process.
• Other actions :
• Plays a role in sexual arousal and satisfaction in
males and nonlactating females.
Neuro-humeral reflex for OT
Anterior pituitary hormones