Hypothalamic & Pituitary Hormones

 Most body functions are controlled by two systems:

namely the nervous system & the endocrine system.
 The endocrine system is composed of a number of
glands that secrete chemicals called hormones
directly in blood stream that affect body functions.ie
they are ductless glands.
 The control of metabolism, growth & reproduction is
mediated through a combination of neural & endocrine
systems located in hypothalamus & pituitary glands.
The Endocrine Glands
Control of petuitary hormones by Hypothalamus
 Hypothalamic Hormones
 Are called releasing factors or hormones.
 Regulate secretion of anterior pituitary hormones.
Some are used for diagnosis or treatment of some
diseases.They include:
1-GH-releasing factor or hormone-also called somatorelin)
 Main function is to stimulate AP to release GH.
 An analogue called sermorelin is used as a diagnostic
test for GH secretion
2-Somatostatin inhibits release of GH &TSH from
anterior pituitary & insulin& glucagon from pancreas,
also deceases release of most GIT hormones & acid.
 Octreotide is a long-acting analogue used to treat
acromegally,carcinoid tumors & tumors secreting
 vasoactive intestinal peptide,glucagonomas & various
pituitary adenomas. Lanreotide is an other analogue
that is used also for thyroid tumors.
3- Thyrotrohpin-releasing hormone(TRH- protirelin)
 Stimulates release of TSH from anterior piuitary.
Protirelin is a synthetic analogue used for diagnosis
of thyroid disorders.
4-Corticotropin-releasing factor (CRF) or hormone
 Releases ACTH & β endorphin from anterior pituitary.Acts
synergistically with antidiuretic hormone (Vasopressin).
 Both its action and release are inhibited by glucocorticoids
 Synthetic preparations were used to test ability of pituitary to
secrete ACTH and to assess whether ACTH deficiency is due to
pituitary or hypothalamic defect.
 5-Gonadotropin releasing hormone(GnRH) and
analogs:
 Drugs available include gonadorelin (natural hormone).
 Long-acting analogs: histrelin (Suprelin), leuprolide
(Leupron), gosrelin (Zoladex), triptorelin(Trelstar), and
nafarelin (Synarel).
 Gonadorelin is used for induction of ovulation in infertility
 Long acting analogs are used for treatment of
endometriosis, prostate cancer, and central precocious
puberty. Experimental use as male contraceptive.
 GnRH antagonists – ganirelix (Antagon) and cetrorelix
(Cetrotide)
 Used to inhibit premature LH surges prior to harvesting eggs
for in vitro fertilization
 Also abarelix (Plenaxis) – a GnRH receptor antagonist used
to treat advanced prostate cancer. Danger of life-
threatening allergic reactions in 4% of patients.
 The Pituitary Gland:
 Consists of two lobes:
-The anterior lobe(adenohypophysis) secretes
GH,TSH,ACTH, FSH,LH & PRL
-The posterior lobe(neurohypophysis)secretes
oxytocin & vasopressin.
 Drugs that mimic or block effects of pituitary or
hypothalamus hormones are used in:
-Replacement therapy for hormonal deficiency.
-As antagonists for diseases due to production of
excess pituitary hormones.
-As diagnostic tools for many endocrine diseases
Pituitary Hormones
 Pituitary Control
 The pituitary is controlled by releasing factors
(hormones) from hypothalamus, these are:
-growth hormone releasing hormone(GHRH)
-corticotropin releasing hormone(CRH)
-gonadotropin releasing hormone(GnRH)
-thyrotropin releasing hormone(TRH)
 Also pituitary hormones & their releasing factors from
hypothalamus are subject to control by the hormones
they regulate their secretion, namely T3,T4,cortisol &
sex hormones (estrogens & progesterone).This is
called negative feedback control.
 The hypothalamus secretes two hormones that
regulate release of GH, these are GHRH that
stimulates GH production & somatostatin(SST)
which inhibits its production.
 GH and its peripheral mediator insulin-like
growth factor -1(IGF-1) inhibit release of GH by
a negative feedback mechanism also.
 Production of prolactin by AP is inhibited by
dopamine & dopamine analogs acting on D2
receptors.
 No hypothalamic regulator for PRL production or
release.
 Anterior pituitary hormones include:
-Growth hormone(GH, somatotropin)
-Thyroid stimulating hormone(TSH,thyrotopin)
-Follicle stimulating hormone(FSH)
-Lutinizing hormone(LH)
-Adrenocorticotrophic hormone(ACTH)
-Prolactin (PRL)
 All anterior pituitary hormones,except prolactin,
are trophic hormones i.e. they regulate
production of other hormones produced by other
endocrine glands & promote growth of these glands.
Mechanism of Action:

 TSH,FSH,LH,and ACTH all act through G

protein coupled receptors, while GH and
PRL act through JAK/STAT superfamily
receptors
 1- Growth Hormone(GH,Somatotropin)
 A single chain polypeptide hormone of 191 aa.
 Secretion is high in the new born,decreasing at 4yrs to
an intermediate level, maintained until after puberty,
then further declines.Secretion is high during sleep.
 Secretion is inhibited by somatostatin & IGF-1.
 Significant differences in amino acid sequence
between humans & other species prevent the use of
non-human hormone.
 Actions:is required in children & adolescents for
attainment of normal adult size.
 Also has important effects on CHO & lipid metabolism & lean
body mass( protein anabolism, lipolysis, glycogenolysis)
 Effects are mediated through IGF-1 (somatomedin- c)
 Congenital or aquired deficiency in children
leads to failure to attain normal adult
size(dwarfism), disproportionate increased
body fat & decreased muscle mass.
 Increased release of GH before closure of
epiphysis leads to gigantism.
 Deficiency leads to short stature, adposity,
hypoglycemia due to unopposed action of
insulin.
Growth Hormone
Physiological Actions:
 Promotes growth of bone& muscle
 Has anabolic effects in
muscle & catabolic effects in
lipid cells, shifting the balance
of body mass to an increase
in muscle mass and reduction
in lipids.
 Promotes use of lipids for
energy production instead of
CHO
 Reduces insulin sensitivity
leading to hyperinsulinemia
 Effects mediated through IGF-
 Growth Hormone
 Physiological actions:
Mechanism – GH receptor stimulation
activates an intracellular tyrosine kinase,
JAK/STAT cytokine superfamily type
recepors, resulting in phosphorylation of
proteins and gene regulation.
Growth-promoting effect is mediated through
production of IGF-1 in liver,bone,muscle &
kidneys.
Growth:almost all body tissues are stimulated
to grow.
Nitrogen metabolism: – increased nitrogen
retention, amino acid transport into tissues,
and incorporation into protein
Carbohydrate and lipid metabolism: –
GH appears to promote use of lipids as
energy source instead of carbohydrates.
GH & IGF-1 have opposite effects on
insulin sensitivity.
GH reduces insulin sensitivity leading to
hyperinsulinemia
IGF-1 lowers serum glucose and
reduces circulating insulin through
action on IGF-1 receptors and insulin
receptors.
 Growth Hormone
Physiological actions (cont..)
 Conserves muscle at the expense of fat during
stress
 Insulin-like growth factor-1 (IGF-1& IGF-2,
somatomedins): are peptides produced by liver and
other tissues in response to GH; appear to mediate
many GH effects.

 Some children with growth failure have severe

IGF-1deficiency that is not responsive to exogenous
GH may be due to mutation in GH receptor or
development of antibodies to GH.
 rhIGF-1 (mecasermin, Increlix) is now available for
treatment of growth failure in GH-resistant patients
Growth Hormone
 Clinical applications – one of the few pituitary
hormones with long-term therapeutic utility.
Recombinant human growth hormone (rhGH,
somatropin) is used clinically. There are two
forms, somatropin and somatrem.
 Hypopituitary dwarfism: – in children with
insufficient GH secretion, GH will generally
produce an increased growth rate over
several years.
 Recently, FDA approved its use in children
with idiopathic, non-GH-deficient short
stature.
 Growth Hormone
 Clinical applications cont…
 Treatment of AIDS – associated wasting
 Treatment of adult onset growth hormone deficiency.
 Turner’s syndrome a genetic disease that occurs in girls, in
combination with gonadotropins.
 Prader –Willi syndrome a genetic disease due to GH
deficiency, is associated with growth failure, obesity and
carbohydrate intolerance.GH decreases body fat &
increases lean body mass,linear growth & energy
expenditure.
 Idiopathic short stature
 Anti-aging supplements – OTC supplements which suggest
they contain hGH. Contain amino acids that are supposed to
release GH.
Growth Hormone
 Problems associated with therapy
– possibility of intracranial hypertension and
visual changes exist, so fundoscopic exams
needed.
 Also possibility of type 2 diabetes and
respiratory difficulties in patients with obesity
or sleep apnea due to Prader-Willi syndrome.
 Possible contamination of human-derived GH
with Creutzfeldt-Jakob virus,thus recombinant
form, somatropin is preffered.
Growth Hormone
 Acromegaly – hypersecretion of GH in adults
after closure of epiphysis, may result in
acromegaly.
 Octreotide (Sandostatin) or other somatostatin
analogs are most commonly used to decrease
GH secretion in these patients.
 Dopamine agonists such as bromocryptine
will inhibit GH secretion from some GH secreting
tumors.
 Pegvisomant (Somavert), a GH receptor
antagonist, is now available to treat acromegaly
in patients who have not responded to other
treatment. Pegvisomant prevents GH
stimulation of IGF-1 production.25/10/2016
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