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The Neuroendocrine System: An Overview
Kent T. Keyser, Ph.D.
Worrell Building
Room 626
975-7225
[email protected]
Overview:
1. Anatomy of the Hypothalamus
Subdivisions of the hypothalamus
2. Anatomy of the Pituitary
Anterior pituitary
Posterior pituitary
Anatomical relationships between hypothalamus and pituitary
3. Function of the Hypothalamus
Autonomic regulation – vasomotor tone, heart rate and blood pressure
Emotional control – emergency responses to stress
Osmoregulation – blood osmolality, water balance, drinking and salt appetite
Thermoregulation – body temperature, thermogenesis
Energy balance – feeding, digestion, and metabolic rate
Biological rhythm – biological clock
Sexual differentiation, reproduction function and behavior, pregnancy and
lactation
Neuroendocrine function - control secretion of hormones from pituitary
4. Neuroendocrine Control of Pituitary Hormones
The hypothalamic-pituitary unit
Hypophyseotropic hormones of the hypothalamus
Regulation of oxytocin and vasopressin secretion from posterior pituitary
Regulation of growth hormone, thyrotropin, corticotropin, gonadotropin and
prolactin secretion from anterior pituitary
Feedback mechanisms - examples
The hypothalamus – is located below (hypo) the thalamus
- Controls the 4 F’s…fighting, fleeing, feeding, and… reproduction
A central autonomic network integrates visceral sensory
information and coordinates autonomic output. The hypothalamus
is a key component. The hypothalamus forms the floor and ventral
walls of the 3rd ventricle and is continuous through the
infundibular stalk of the posterior pituitary.
The hypothalamus:
• controls blood flow (cardiac output, vasomotor tone, blood
osmolarity, renal clearance).
• regulates energy metabolism (monitors blood glucose, regulates
feeding, digestive functions, metabolic rate and body temperature).
• regulates reproductive activity (influences gender identity, sexual
orientation, mating behavior, menstrual cycles, pregnancy and
lactation)
•coordinates responses to threatening conditions (controls release
of stress hormones, balance between sympathetic and
parasympathetic activity, and regional blood flow).
Subdivisions of the hypothalamus
Anterior hypothalamic area: depressor (reduction of BP)and thirst,
temperature regulation
Posterior hypothalamic area: pressor (elevation of BP) center, temperature
regulation
Paraventricular nucleus: water balance, oxytocin and vasopressin release
Supraoptic nucleus: osmoregulation, water balance, vasopressin release
Lateral hypothalamic area: feeding center, energy balance
Ventromedial nucleus: satiety center, energy balance
Suprachiasmatic nucleus: circadian rhythms
Preoptic area: sexual differentiation, sexual behavior, reproductive function
Dorsal hypothalamic area: dopaminergic neurons
Arcuate nucleus: dopaminergic neurons
Median eminence: the final common pathway to the pituitary
The hypothalamus is a cluster of about 50 interconnected nuclei.
The hypothalamus integrates autonomic activity and the endocrine system.
Neurons located along The axons secrete peptides directly into the portal
the wall of the 3rd
circulation that supplies the pituitary.
ventricle manufacture
peptides known as
releasing or inhibiting
factors that control the
secretion of hormones by
the anterior pituitary. The
axons of these cells
project to the median
eminence at the
hypothalamus pituitary
junction.
The paraventricular
and and suproptic
nuclei contain
neurosecretory
neurons whose axons
descend into the
posterior pituitary.
These neurons can
also secrete oxytocin
or vasopresson
(antidiurectic) into the
blood.
Hypothalamic releasing factors summary
Anterior pituitary
Factor
Ant. Pit. Target
hormone released
target
GHRH (GH releasing factor)
somatotroph
GH
somatic tissues
TRH (thyrotropin RH)
thyrotroph
TSH
Thyroid cells
CRH (corticotropin RH
Corticotroph
ACTH
Adrenal cortex (steroids)
GnRH (gonadotropin RH)
gonadotroph
FSH; LH
gonads (Leydig cells:
spermatogenesis,
testosterone: ovary
follicular cells: estrogen
and progestin
None (dopamine inhibits)
Lactotroph
PRL
mammary glands (milk)
Hormone released
target
---------------------------------------------------------------
Posterior pituitary
Factor
Post. Pit target
AVP
AVP
collecting duct (increase
H20 permeability
OT
OT
Uterus and breast
Two models for feedback control of
hormone secretion.
A, A sensor (e.g., a beta; cell in a
pancreatic islet) detects some
regulated variable (e.g., plasma
[glucose]) and responds by
modulating its secretion of a hormone
(e.g., insulin). This hormone, in turn,
acts on a target (e.g., liver or muscle)
to modulate its production of another
hormone or a metabolite (e.g.,
glucose), which may affect a second
target (e.g., making glucose available
to the brain). In addition, the other
hormone or metabolite feeds back on
the original sensor cell.
B, Under the influence of the cerebral
cortex, the hypothalamic releases
CRH, which stimulates the anterior
pituitary to release ACTH, which in
turn stimulates the adrenal cortex to
release cortisol. The cortisol acts on a
number of effector organs. In
addition, the cortisol feeds back on
both the anterior pituitary and the
hypothalamus. ACTH,
adrenocorticotropic hormone; CRH,
corticotropin-releasing hormone.
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© 2005 Elsevier
The hypothalamo-pituitary axis. The pituitary
(or hypophysis) is actually two glands-an
anterior pituitary and a posterior pituitary (or
neurohypophysis). In both cases the
hypothalamus controls the secretion of
hormones by the pituitary but the mechanisms
are very different. Anterior pituitary. Smallbodied hypothalamic neurons in several nuclei
that surround the third ventricle (the arcuate,
the paraventricular and ventromedial nuclei,
and the medial preoptic and periventricular
regions) secrete releasing and inhibitory
factors into a rich funnel-shaped plexus of
capillaries that penetrates the median
eminence and surrounds the infundibular
recess. The capillaries coalesce into the long
portal veins and carry the factors to the ant.
pituitary. Posterior pituitary Other cells secrete
into capillaries that make up the short portal
veins and deliver releasing factors to the troph
cells secrete GH, TSH, ACTH, LH, FSH, PRL.
ACTH, adrenocorticotropin hormone; AVP,
arginine vasopressin; FSH, follicle-stimulating
hormone; GH, growth hormone; LH, luteinizing
hormone; OT, oxytocin; PRL, prolactin; TSH,
thyroid-stimulating hormone.
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Circumventricular organs: windows on the brain
Regions of the 3rd and 4th ventricles that the lack blood-brain barrier
These regions are highly vascularized and the capillaries are fenestrated-high molecular weight
substances can pass from blood to brain.
There are specialized cells in these regions, tanycytes, that connect the ventricle to the adjacent
neural tissue
Contains receptors for hormones that control fluid volume, electrolytes, cardiac function
The neurons in these regions project to other areas involved with neuroendocrine and cardiac
control.
Circumventricular organs include, among others, the neurohypophysis (posterior pituitary),
median eminence, area postrema, anterior periventricular region surrounding the 3rd ventricle.
Posterior pituitary. Large neurons in the
paraventricular and supraoptic nuclei of the
hypothalamus synthesize the hormones
AVP and OT. These hormones travel down
the axons of the hypothalamic neurons to
the posterior pituitary where the nerve
terminals release the hormones, like
neurotransmitters, into a rich plexus of
blood vessels. Since the posterior pituitary
is one of the circumventricular organs
where the blood brain barrier is breached,
the secreted vasopressin and oxytocin can
get into the general circulation.
ACTH, adrenocorticotropin hormone; AVP,
arginine vasopressin; FSH, folliclestimulating hormone; GH, growth hormone;
LH, luteinizing hormone; OT, oxytocin; PRL,
prolactin; TSH, thyroid-stimulating
hormone.
Hormones secreted by the pituitary
Major target organ(s)
Major Physiologic
Effects
Growth hormone
Liver, adipose tissue
Promotes growth
(indirectly), control of
protein, lipid and
carbohydrate
metabolism
Thyroid-stimulating
hormone
Thyroid gland
Stimulates secretion of
thyroid hormones
Adrenocorticotropic
hormone
Adrenal gland (cortex)
Stimulates secretion of
glucocorticoids
Prolactin
Mammary gland
Milk production
Luteinizing hormone
Ovary and testis
Control of reproductive
function
Follicle-stimulating
hormone
Ovary and testis
Control of reproductive
function
Vasopressin
Kidney
Conservation of body
water
Oxytocin
Ovary and testis
Stimulates milk ejection
and uterine contractions
Hormone
Anterior
Pituitary
Posterior
Pituitary
Pituitary: the Master Gland of Endocrine System
The GnRH-FSH/LH-Reproductive Hormone Axis
Neurons in the arcuate
nucleus and preoptic area
produce GnRH and release
it near the portal vessels in the
median eminence. The blood
vessels convey it to the gonadotropes
in the anterior pituitary. The release of
GnRh is pulsatile (1/hr) and so there is
corresponding pulsatile release of LH
and FSH. These cause ovarian cells to
produce estrogens and progestin. LH
causes the testes to produce
testosterone and FSH causes the
Sertoli cells to synthesize a number of
products needed by the Leydig cells
and the developing spermatogonia.
The CRH-ACTH-Corticosteroids Axis
ACTH release by is stimulated
by CRH from the PVN. ACTH
is released by the corticotrope
cells in the ant pituitary. In the
adrenal cortex it binds to
melanocortin 2 receptors and
the effect is to simulate the
formation of cortisol. Cortisol
affects the liver (glucose
synthesis) muscle (protein
breakdown to release amino
acids), and adipose tissue to
mobilization of fat).
The TRH/Dopamine-Prolactin Axis
The arcuate nucleus
and perhaps the median
eminence of the hypothalamus
synthesize thyrotropin
releasing hormone which
stimulates the release of
Thyrotrophs
thyrotropin (TSH) from the
thyrotrophs of the anterior
pituitary. This in turn
stimulates the cells of the
thyroid to produce thyroid
hormones that act on many
tissues.
The regulation of prolactin is
very different. The pituitary
secrets PRL at low rates
throughout life in both males
and females. However, its
major function is important
only in females and then only
at specific times. However,
PRL release is controlled.
Without hypothalamic
regulation, PRL would be
secreted at high levels but
release is tonically inhibited by
dopamine (prolactin inhibitory
factor) from the arcuate
nucleus. During breast
simulation, neural afferents
inhibit dopamine release
which relieves the lactotrophs
of the tonic inhibition.
Several factors act as
prolactin releasing
factors. For example,
TRH release from the
hypothalamus is
stimulated by suckling.
In lactating females,
TRH causes increased
milk production.
Estradiol increases the
sensitivity of the
lactotrophs to TRH and
decreases the
sensitivity to dopamine.
Two final points: input
from neurons in the
spinal cord inhibit
neurons in the arcuate
and preoptic areas of
the hypothalamus which
causes a reduction in
the release of GnRH.
This in turn inhibits the
ovarian cycle. In
addition, the input from
cells in the spinal cord
causes increased
synthesis and release of
oxytocin into the
posterior pituitary.
Oxytocin promotes
uterine contractions and
milk ejection.
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© 2005 Elsevier