Growth hormone and prolactin are peptide hormones produced by the pituitary gland. Growth hormone promotes growth and development while prolactin promotes breast development and milk production. Their secretion is regulated by hormones from the hypothalamus such as growth hormone releasing hormone and prolactin inhibiting hormone (dopamine). Abnormal levels can cause diseases - high growth hormone causes gigantism or acromegaly, low growth hormone causes dwarfism, and high prolactin causes infertility. Somatostatin and octreotide inhibit growth hormone and prolactin secretion and are used to treat conditions caused by their excess.

1. GROWTH HORMONE & PROLACTIN
Prajjwal
20PPC013
M. Pharma (Pharmacology)

2. INTRODUCTION
• Growth hormone is a peptide hormone produced by the pituitary gland, that
stimulates development, growth, and regeneration.
• It is made up of 191 amino acids that make a long single-chain peptide of 22000
molecular weight.
• It is synthesized in somatotroph cells found in the anterior pituitary gland.
These cells store and release the hormone.
• GH promotes growth of bones and all other organs by inducing hyperplasia.
Growth of brain and eye is independent of GH.
• GH promotes utilization of fat and spares carbohydrates, glucose uptake by
muscles is reduced while output from liver is enhanced.

3. CONT.…
• There are two types of growth hormones somatotropin and
somatropin.
• Hypersecretion of GH can cause gigantism in children and acromegaly
in adults. Pituitary tumours are also caused due to hypersecretion of
growth hormone in adults.
• Hyposecretion of GH causes dwarfism in children and changes the
cholesterol levels, muscle mass, and bone strength in adults.

4. ACTION & REGULATION OF SECRETION
• The hypothalamus produces GH releasing hormone (GHRH) as well as inhibitory hormones
somatostatin (SST).
• Ghrelin, a peptide hormone secreted from the stomach binds to receptors on somatotrophs
and potently stimulates secretion of growth hormone.
• Receptors for GHRH and somatostatin are G protein coupled receptors (GPCR) which can
enhance or inhibit GH secretion by increasing or decreasing cAMP formation respectively in
pituitary somatotrophs.
• GH acts directly to induce lipolysis in adipose tissue,
gluconeogenesis and glycogenesis in liver and decrease
glucose utilization by muscles.
• The growth promoting, nitrogen retaining and certain
metabolic action of GH are exerted indirectly through the
elaboration of peptide called Insulin-like growth factors (IGF-1).

5. CONT....
• IGF-1 cause an negative feedback
inhibition effect on growth hormone
secretion by stimulating somatostatin
release from the hypothalamus.
• Stimuli that cause GH release are fasting,
hypoglycemia, exercise, stress, sleep, and
i.v. infusion of arginine.

6. PREPARATION & USE
• The primary indication for GH is pituitary dwarfism. 0.03 to 0.06 mg/kg daily in
the evening or on alternate days.
• Human GH produced by recombinant DNA techniques (rhGH) called somatropin is
available for clinical use.
• Somatropin has been tried in children with constitutional short stature with
encouraging results.
• In adults GH deficient patients, rhGH 150-300 μg/day is given subcutaneously,
adjusted later according to response.
• It should not be given to postoperative, trauma, cancer and other critically ill
patients.
• It is one of the drugs included in dope testing.

7. ADVERSE EFFECT
• Somatotropin has low immunogenicity, allergic reactions or resistance
to treatment are not a problem.
• Pain at injection site, lipodystrophy, glucose intolerance,
hypothyroidism, salt and water retention, hand stiffness, headache are
possible adverse effects.
• Rise in intracranial tension occurs in few cases.

8. GH INHIBITORS (SOMATOSTATIN)
• This is a 14 amino acid peptide that inhibit the secretion of GH, prolactin, and TSH
by pituitary gland. Insulin and glucagon by pancreas.
• The g.i. action produces steatorrhoea, diarrhoea, hypochlorhydia, and nausea as
side effects.
• The decreased g.i. mucosal blood flow can be utilized for controlling bleeding
esophageal varices and bleeding peptic ulcer, but octreotide is preferred now due
to longer duration of action.
• Somatostatin is used in acromegaly is limited because its short duration of action.
• Dose for upper g.i. bleeding – 250 μg slow iv injection over 3 min followed by 3 mg
iv infusion over 12 hours.

9. OCTREOTIDE
• Octreotide, a synthetic octapeptide surrogate of somatostatin, 40 times
more potent in suppressing GH secretion and longer acting.
• Used in diarrhoea due to suppression of hormones which enhance
intestinal mucosal secretion.
• Adverse effects are abdominal pain, nausea, steatorrhoea, and gall
stones.
• Dose, initially 50-100 μg s.c. twice daily, increased up to 200 μg.
• It injected i.v. (100 μg) to reduce hepatic blood flow and helps stop
esophageal variceal bleeding.

10. PROLACTIN
• It is 199 amino acid, single chain peptide of MW 23000, quite similar
chemically to GH.
• It is secreted from the anterior pituitary by lactotroph cells. These are
abundant in the gland and increase in number during pregnancy, under the
influence of estrogen.
• Prolactin was originally described as the hormone which causes secretion of
milk from crop glands of pigeon and later found in human beings as well.
• Prolactin is the primary stimulus which in conjugation with estrogen,
progesterone and several other hormones, cause growth and development of
breast during pregnancy.

11. CONT….
• Prolactin suppress hypothalamo-pituitary-gonadal axis by inhibiting
GnRH release.
• High level of prolactin during breastfeeding is responsible for
lactational amenorrhea, inhibition of ovulation and infertility for
several months postpartum.
• Prolactin receptor is expressed on the surface of target cells, structurally
and functionally similar to GH receptor.
• Placental lactogen and GH also bind to prolactin receptor but prolactin
does not bind to GH receptor.

12. REGULATION OF SECRETION
• Prolactin is under predominant inhibitory
control of hypothalamus through PRIH/PRIF
(dopamine) that acts on pituitary lactotroph
D2 receptors.
• Dopaminergic agonists are bromocriptine,
cabergoline, quinagolide.
• Dopaminergic antagonists are chlorpromazine,
haloperidol, metoclopramide.
• Thyrotropin releasing hormone (TRH),
prolactin releasing peptide, and vasoactive
intestinal peptide (VIP) can stimulate prolactin
secretion.

13. CAUSES OF HYPER PROLACTINEMIA
Hyperprolactinemia is responsible for the infertility syndrome in women. In males it
causes loss of libido and depressed fertility.
CAUSES –
• Disorders of hypothalamus removing the inhibitory control over pituitary.
• Antidopaminergic and DA depleting drugs.
• Prolactin secreting tumours.
• Hypothyroidism with high TRH levels.

14. PROLACTIN INHIBITORS (BROMOCRIPTINE)
• It is an synthetic ergot derivative 2-bromo-α-ergocryptine, a potent dopamine
agonist.
• It has greater action on D2 receptors while at certain dopamine sites in the brain it
acts as a partial agonist.
• It decrease prolactin release from pituitary by activating dopaminergic receptors on
lactotroph cells.
• Increase GH release in normal individuals, but decrease the same from pituitary
tumors that cause acromegaly.
• Has levodopa like actions in CNS, can produces nausea and vomiting by
stimulating dopaminergic receptors.

15. PHARMACOKINETICS
• Only 1/3 part is absorbed of an oral dose.
• Bioavailability is further lowered by high first pass metabolism in liver.
• Metabolites excreted in bile.
• Plasma t1/2 is 3-6 hours.
USES
• Always started at low dose (1.25 mg BD) and then gradually increased till response
occurs.
• To treat hyperprolactinemia.
• Treat acromegaly due to small pituitary tumours.
• Treat parkinsonism, similar to levodopa.

16. SIDE EFFECTS
• Side effects are frequent and dose related.
• Early side effects are; nausea, vomiting, constipation, nasal blockage.
Postural hypotension may be marked at the initiation of therapy.
• Late side effects are; behavioural alteration, mental confusion,
hallucination, psychosis.

17. THANK-YOU