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AND PITUITARY
HORMONES
Functional Anatomy of the
Hypothalamus and Pituitary Gland
Pituitary Gland
HYPOTHALAMIC
HORMONES
HYPOTHALAMIC HORMONES
Controls the release of pituitary hormones
Hypothalamic hormones are released from
the hypothalamic nerve fiber endings
around the capillaries of the hypothalamic-
hypophysial system in the pituitary stalk
Released in a pulsatile manner
Growth-hormone-releasing
hormone (GHRH)
Also known as growth-hormone-releasing
factor (GRF or GHRF) or somatocrinin
a 44-amino acid peptide hormone
produced in the arcuate nucleus of the
hypothalamus
GHRH is released from neurosecretory
nerve terminals of these arcuate neurons,
and is carried by the hypothalamo-
hypophysial portal circulation to the
anterior pituitary gland where it stimulates
growth hormone secretion
The actions of GHRH are opposed by another
hypothalamic hormone, somatostatin, also
known as "growth-hormone-inhibiting hormone"
(GHIH).
Somatostatin is released from neurosecretory
nerve terminals of periventricular somatostatin
neurons, and is carried by the hypothalamo-
hypophysial portal circulation to the anterior
pituitary where it inhibits GH secretion by
hyperpolarising the somatotropes.
• Somatostatin and GHRH are secreted in
alternation, giving rise to the markedly
pulsatile secretion of GH. However
recently it had been discovered that
somatostatin does not affect the secretion
of GH
The amino acid sequence of GHRH is:
Tyr - Ala - Asp - Ala - Ile - Phe - Thr - Asn - Ser -
Tyr - Arg - Lys - Val - Leu - Gly - Glu - Leu - Ser -
Ala - Arg - Lys - Leu - Leu - Gln - Asp - Ile - Met -
Ser - Arg - Glu - Gln - Gly - Glu - Ser - Asn - Gln -
Glu - Arg - Gly - Ala - Arg - Ala - Arg - LeuNH2
Somatostatin
a peptide hormone that regulates the
endocrine system and affects
neurotransmission and cell proliferation via
interaction with G-protein-coupled
somatostatin receptors and inhibition of the
release of numerous secondary hormones
Somatostatin
has two active forms produced
by alternative cleavage of a
single preproprotein: one of 14
amino acids, the other of 28
amino acids. Somatostatin
Somatostatin is secreted not only
by cells of the hypothalamus but
also by delta cells of stomach,
intestine, and pancreas. It binds
to somatostatin receptors.
Octreotide
Octreotide
is an octopeptide that mimics natural
somatostatin pharmacologically, though is
a more potent inhibitor of growth hormone,
glucagon, and insulin than the natural
hormone
Somatostatin is classified as an inhibitory hormone, whose main actions
are to:
•Inhibit the release of growth hormone (GH)
•Inhibit the release of thyroid-stimulating hormone (TSH)
•Suppress the release of gastrointestinal hormones
•Gastrin
•Cholecystokinin (CCK)
•Secretin
•Motilin
•Vasoactive intestinal peptid (VIP)
•Gastric inhibitory polypeptide (GIP)
•Enteroglucagon (GIP)
•Lowers the rate of gastric emptying, and reduces smooth muscle
contractions and blood flow within the intestine.
•Suppress the release of pancreatic hormones
•Inhibit the release of insulin
•Inhibit the release of glucagon
•Suppress the exocrine secretory action of pancreas
Somatostatin opposes the effects of Growth Hormone-Releasing
Hormone (GHRH)
Corticotropin-releasing hormone
(CRH)
originally named corticotropin-releasing
factor (CRF), and also called
corticoliberin, is a polypeptide hormone
and neurotransmitter involved in the stress
response
Corticotropin-releasing hormone
(CRH)
produced by neuroendocrine cells in the
paraventricular nucleus of the hypothalamus
The portal system carries the CRH to the
anterior lobe of the pituitary, where it stimulates
corticotropes to secrete corticotropin (ACTH)
and other biologically active substances (for
example β-endorphin).
Corticotropin-releasing hormone
(CRH)
Role in parturition
CRH is also synthesized by the placenta
and seems to determine the duration of
pregnancy
Corticotropin-releasing hormone
(CRH)
The 41-amino acid
sequence of CRH was
first discovered in
sheep by Vale et al in
1981 Its full sequence
is
SQEPPISLDLTFHLLR
EVLEMTKADQLAQQA
HSNRKLLDIA
Thyrotropin-releasing hormone
(TRH)
also called thyrotropin-releasing factor
(TRF), thyroliberin or protirelin, is a
tripeptide hormone that stimulates the release
of thyroid-stimulating hormone and prolactin
by the anterior pituitary
TRH is produced by the hypothalamus and
travels across the median eminence to the
pituitary via the hypophyseal portal system
Thyrotropin-releasing hormone
(TRH)
In addition to the brain, TRH can also be
detected in other areas of the body including
the gastrointestinal system and pancreatic
islets
Medical preparations of TRH are used in
diagnostic tests of thyroid disorders
It is used in pharmacology to test the
response of the anterior pituitary gland and in
acromegaly
Thyrotropin-releasing hormone
(TRH)
The sequence of TRH was first determined and
the hormone synthesized by Roger Guillemin
and Andrew V. Schally in 1969. Its molecular
weight is 359.5 Da and its structure is:
(pyro)Glu-His-Pro-NH2
Gonadotropin-releasing
hormone 1 (GNRH1)
• is a peptide hormone responsible for the release of
FSH and LH from the anterior pituitary
• GNRH1 is synthesized and released by the
hypothalamus
• GnRH was previously called LHRH (luteinizing
hormone-releasing hormone)
Gonadotropin-releasing
hormone 1 (GNRH1)
The gene, GNRH1, for the
GNRH1 precursor is
located on chromosome 8.
This precursor contains 92
amino acids and is
processed to GNRH1, a
decapeptide (10 amino
acids) in mammals.
pyroGlu-His-Trp-Ser-Tyr-
Gly-Leu-Arg-Pro-Gly
CONH2.
Gonadotropin-releasing
hormone 1 (GNRH1)
GNRH1 is considered a neurohormone, a
hormone produced in a specific neural cell and
released at its neural terminal
A key area for production of GNRH1 is the
preoptic area of the hypothalamus, that
contains most of the GNRH1-secreting
neurons. GNRH1 is secreted in the
hypophysial portal bloodstream at the median
eminence
Gonadotropin-releasing
hormone 1 (GNRH1)
The portal blood carries the GNRH1 to the
pituitary gland, which contains the gonadotrope
cells, where GNRH1 activates its own receptor,
gonadotropin-releasing hormone receptor
(GNRHR), located in the cell membrane
GNRH1 is degraded by proteolysis within a few
minutes.
Gonadotropin-releasing
hormone 1 (GNRH1)
In males, GNRH1 is secreted in pulses at
a constant frequency, but in females the
frequency of the pulses varies during the
menstrual cycle and there is a large surge
of GNRH1 just before ovulation.
Gonadotropin-releasing
hormone 1 (GNRH1)
GNRH1 activity is very low during
childhood, and is activated at puberty
During the reproductive years, pulse
activity is critical for successful
reproductive function as controlled by
feedback loops
However, once a pregnancy is
established, GNRH1 activity is not
required
Dopamine
In the brain, dopamine functions as a
neurotransmitter, activating dopamine receptors
Dopamine is also a neurohormone released by the
hypothalamus
Its main function as a hormone is to inhibit the
release of prolactin from the anterior lobe of the
pituitary
Dopamine has the chemical formula (C6H3(OH)2-
CH2-CH2-NH2)
Its chemical name is 4-(2-aminoethyl)benzene-1,2-
diol and it is abbreviated "DA."
PITUITARY
HORMONES
GROWTH HORMONE (GH)
Also called somatropin or somatotropin
Synthesized in somatotropes, a subclass of the
pituitary acidophilic cells
The genes for human growth hormone are
localized in the q22-24 region of chromosome 17
Disulfide bonds
GROWTH HORMONE (GH)
Peptides released by neurosecretory
nuclei of the hypothalamus into the portal
venous blood surrounding the pituitary are
the major controllers of GH secretion by
the somatotropes.
GROWTH HORMONE (GH)
Growth hormone releasing hormone
(GHRH) from the arcuate nucleus of the
hypothalamus and ghrelin* promote GH
secretion, and somatostatin from the
periventricular nucleus inhibits it.
Secretes GHRH
Ghrelin is a hormone produced by P/D1 cells
lining the fundus of the human stomach that
stimulate appetite
Ghrelin levels increase before meals and
decrease after meals
It is considered the counterpart of the hormone
leptin, produced by adipose tissue, which
induces satiation when present at higher levels.
Much of the growth hormone in the
circulation is bound to a protein (growth
hormone binding protein, GHBP) which is
derived from the growth hormone receptor
Growth hormone receptor is a member of
the cytokine receptor superfamily.
One growth hormone molecule binds to
one receptor and then recruits a second
receptor to form a dimer through which
signalling occurs.
The effects of growth hormone on the
tissues of the body can generally be
described as anabolic
Height growth in childhood is the best known
effect of GH action, and appears to be
stimulated by at least two mechanisms:
A Na+/K+-ATPase-driven pump
concentrates iodide (I-) in thyroid
cells, and the iodide is transported
to the follicle lumen
In the follicle lumen, it is oxidized by a
thyroperoxidase found only in thyroid
tissue.
Thiourea drugs, which are antithyroid
drugs, act on this step
The addition of oxidized iodide to tyrosine
residues of thyroglobulin is catalyzed by
the same thyroperoxidase enzyme,
leading to the production of thyroglobulin
containing monoiodotyrosyl (MIT) and
diiodotyrosyl (DIT) residues. This
reaction is called organification.
The thyronines, T3 and T4, are formed by
combining MIT and DIT residues on thyroglobulin
in a process called coupling
The thyroid is the only tissue that can oxidize I– to
a higher valence state, an obligatory step in I–
organification and thyroid hormone biosynthesis
Mature, iodinated thyroglobulin is
taken up in vesicles by thyrocytes
and fuses with lysosomes
Lysosomal proteases degrade
thyroglobulin releasing amino acids
and T3 and T4, which are secreted into
the circulation
(Organification)
Thiourea
drugs