Transcript 5104_a1

NSC 5404 : Session 1
Hypothalamus and its
regulation of anterior and
posterior pituitary secretions
Leo Renaud, MD PhD
Professor, Medicine & Neurology,
University of Ottawa
Associate Director & Senior Scientist, OHRI
Pituitary and Hypothalamus
Where & what is the
hypothalamus?
Some developmental notes:
Anterior pituitary (adenohypophysis) forms from
the roof of the pharynx in the embryo.
Posterior pituitary develops from the floor of the
third ventricle forming the stalk (infundibulum)
and the posterior pituitary (neurohypophysis).
Anterior pituitary has no neurons or synapses, just
cells producing hormones such as growth hormone,
leuteinizing hormone, follicle stimulating hormone,
thyroid stimulating hormone, adrenocorticotropic
hormone.
Infundibulum contains axons from hypothalamic neurons
that project into the posterior pituitary where they
terminate near capillaries. These terminals contain
hormones oxytocin and vasopressin.
Introduction to the Pituitary and Hypothalamus
Pituitary and hypothalamus utilize synaptic communication as well as
hormonal communication to regulate target cells.
Pituitary and hypothalamus are the link between the nervous system and
the endocrine system.
Hypothalamus is also major regulator of body homeostasis
1. Homeostatic control includes regulating hunger, thirst, sex drive,
sleep-wake cycles, body temperature, blood glucose.
2. Endocrine control via regulating the release of pituitary hormones.
3. Autonomic control via descending pathways to sympathetic and
parasympathetic preganglionic neurons.
4. Limbic function via connections to limbic system regulating emotional
behavior.
Functions of Selected Regions of Hypothalamus
Suprachiasmatic nucleus: THE biological clock, regulates circadian rhythms.
Lateral hypothalamus: feeding and arousal (orexinergic cells).
Ventromedial nucleus: a “satiety center”, inhibits hunger.
Anterior hypothalamus: contains osmoreceptors, triggers thirst
Thermoregulation involves several systems including sweat glands,
vasodilation/vasoconstriction, skeletal muscles involved in shivering
and panting, and endocrine systems that control metabolic rate.
Preoptic area (POA) detects increased body temp and activates systems
that dissipate heat; lesions here cause hyperthermia.
Posterior HT functions to conserve heat; lesions here cause
poikilothermia, where body temp matches environment temp.
More recent studies suggest HT functions in sexual desire/sex preference.
A ‘global’ view of hypothalamic pituitary
functions
Hypothalamus: regulator of the endocrine system
Figure 18.1
Three Methods of Hypothalamic Control over the Endocrine
System
Figure 18.5
Anatomy of the pituitary gland
Anatomy and Orientation of the Pituitary Gland
The Hypophyseal
Portal System
Hypothalamic Control of the
Anterior Pituitary
• Hormonal control
mechanism
• Hypothalamic neurons
synthesize releasing and
inhibiting peptide
hormones.
• These are transported to
axon endings in the
median eminence where
they are secreted into the
hypothalamo-hypophyseal
portal system to reach
receptors that regulate the
secretions of anterior
pituitary hormones
How does the neuroendocrine axis work?
• Hypothalamic parvicellular neurons synthesize releaseor release-inhibiting “factors” or “hormones” (peptides)
• Packaged in secretory granules, transported in axons to
nerve terminal storage sites
• On demand, neurons depolarize, prompting frequencydependent exocytosis into the median eminence
capillaries of the pituitary portal vessels
• Transported as “hormones” to the anterior pituitary
where they exit to the extracellular space
• Attach to specific G-protein coupled receptors on target
cells, triggering exocytosis of appropriate “hormones”
that seek their peripheral glandular targets
Anterior Pituitary
Thyroid-Releasing Hormone
The anterior pituitary is
actually a glandular
structure, composed of
diverse cell types that
synthesize specific hormones
to control specific peripheral
glands or tissues:
►luteinizing hormone (LH)
and follicle stimulating
hormone (FSH) that regulate
ovarian function;
►thyroid stimulating hormone
(TSH) to regulate thyroid
function;
►adrenocorticotrophic
hormone (ACTH) to regulate
adrenal cortex function;
►growth hormone (GH) for
bone and muscle;
►prolactin to stimulate milk
production in the breast. :
Adenohypophysis: LM histology
Adenohypophysis: EM histology
GnRH
GONADOTROPIC CELL
B
Gq
P q
L
C q
GnRH receptor
Ca2+
DAG

PIP2
CAM
IP3
Ca2+
Ca2+
Y
CAMdependent
kinase
SER
Storage
vesicle
Protein
kinase C
Protein
phosphorylation
Ca2+

FSH
LH
Figure 6. In the gonadotropes GnRH causes release of LH and FSH (B)
Feedback control of Endocrine Secretion
Feedback control of Endocrine Secretion
Some clinical conditions that may arise
due to altered feedback or lack of
hormone regulation
• Too much / too little thyroxine (T4) and triiodothyronine (T3) results in hyper /
hypothyroidism respectively
• To much growth hormone secretion causes a
condition called acromegaly
• Excessive adrenal glucocorticoid secretion can
produce Cushing’s syndrome
Symptoms of excess circulating thyroid hormones
[thyroxine (T4) and triiodothyronine (T3)]
fine tremor, heat intolerance, sweaty skin, exophthalmos,
possible thyroid enlargement (goitre).
Excess Growth Hormone secretion
→ Acromegaly
Clinical features of excessive
secretion of cortisol
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Truncal obesity
Moon facies
Abdominal striae
Osteoporosis
Acne
Easy bruising
Hirsutism
Hypertension
Hyperglycemia