2. Introduction
• The control of metabolism, growth and reproduction is mediated by a combination of
neural and endocrine system located in the hypothalamus and pituitary gland
• The pituitary weighs 0.6g and rest on the base of the brain in the Sella turcica near the optic
chiasma and cavernous sinuses
• It is connected to the overlying hypothalamus by a stalk of neurosecretory fibres and
blood vessels including portal venous system that drains the hypothalamus and perfuses
the anterior pituitary
3. Introduction
• Cells in the anterior pituitary gland also secrete small amounts of a
variety of other proteins, including renin, angiotensinogen,
sulfated proteins, fibroblast growth factor, and other mitogenic
factors.
• There are two posterior pituitary hormones: Vasopressin and
oxytocin. Both are synthesized in the neuronal cell bodies of
hypothalamus and transported via their axon to the posterior
pituitary
4.
5. Growth Hormones
• A protein that stimulates linear body growth in children and regulates
cellular metabolism in both adults and children
• Growth hormone stimulates lipolysis, enhances production of free fatty
acids, elevates blood glucose, and promotes positive nitrogen balance
• Many of its anabolic actions are mediated by enhanced production of an
insulin-like growth factor (IGF-1) a protein produced in many tissues in
response to growth hormone
6. Growth Hormone
• Serum levels between bursts of release are usually low (5ng/mL)
and increase more than 10-fold when release is elevated
• The marked variation in serum levels is in part the result of strong
controls in opposite directions by the hypothalamic hormones,
growth hormone–releasing hormone (GHRH) and somatostatin
• Growth hormone is a 191 – amino-acid peptide with two sulfhydryl
bridges. It closely resembles prolactin
7. Growth Hormones
• In the past, medicinal GH was isolated from the pituitary of human cadaver
• However, this form of GH was found to be contaminated with prions that could
cause Creutzfeldt-Jakob disease
• The primary peripheral mediator of GH is insulin like growth factor 1 (IGF-1) or
Somatomedin C
8. Growth Hormone (Agonist)
1. SOMATROPIN
• Mechanism of action: Recombinant form of human GH acts through GH
receptors (JAK/STAT receptor superfamily) to increase production of IGF-1
• Restores normal growth and metabolic GH effects in GH-deficient individuals
• Increases final adult height in some children with short stature not due to GH
deficiency (Idiopatic short stature)
• Replacement of GH in deficiency states especially those associated congenital
anomalies like Noonan syndrome, Prader-willi syndrome, turner’s syndrome, short
stature homobox containing gene
9. Growth Hormones
• Chronic renal insufficiency. Pre transplant, growth deficiency in adult, Wasting in
HIV patients, Short bowel syndrome to improve GIT function, Popular in some
“anti-aging” and “anti-obesity” programs
• It is a subcutaneous injection administered 6 – 7 times a week, peak level within 2-4
hours and persist for 36 hours
• Toxicity: Pseudotumor cerebri, oedema, progression of scoliosis, risk of asphyxia in
severely obesed patients with prader-willis syndrome and upper air way obstruction
or sleep apnea, hyperglycemia, slipped capital femoral epiphysis
10. Growth Hormones
1. Mecasermin (IGF-1 Agonist)
• Mechanism of action: Recombinant form of IGF-1that stimulates IGF-1
receptors
• Effects: Improves growth and metabolic IGF-1 effects in individuals with IGF-1
deficiency due to severe GH resistance
• Clinical application: Replacement in IGF-1 deficiency that is not responsive to
exogenous GH
• Administered subcutaneously
• Toxicity: Hypoglycemia, intracranial hypertension, increased liver enzymes
11. Growth Hormone (Antagonist)
1. Somatostatin analogs
• Somatostatin is a 14- amino-acid peptide found in the hypothalamus , CNS, pancreas
and GIT
• Inhibits the release of GH, TSH, glucagon, insulin and gastrin
• Exogenous somatostatin is rapidly cleared from the circulation (half life of 1 – 3
minutes) by the kidneys
• Has limited therapeutic usefulness because of short duration of action and multiple
effects on organs
• Long acting somatostatin analogs that have been developed areoctreotide and
Lantreotide
12. Growth Hormone (Antagonist)
OCTREOTIDE: (Somatostatin analog)
• Mechanism of action: Agonist at somatostatin receptor site
• Effects: Inhibits production of GH and to a lesser extent TSH, glucagon, Insulin,
gastrin
• Clinical application: Acromegalymand several hormone-secretingn tumour,
acute control of bleeding from esophageal varices
• Subcutaneous or IV injection, long acting formulation injected IM monthly
• Toxicity: GIT disturbance, gallstones, bradycardia, cardiac conduction problems
13. Growth Hormone (Antagonist)
1. GH receptor antagonist (PEGVISOMANT)
• It is a polyethylene glycol (PEG) derivative of a mutant GH
• Like normal GH, it has two binding sites but with differential affinity
• Mechanism of action: Blocks GH receptors
• Effects: Ameliorates effects of excess GH production
• Clinical application: Acromegaly
• Subcutaneous injection
• Toxicity: Increased liver enzymes
14. GONADOTROPINS (FSH, LH, HCG)
• All are produced by a single type of pituitary cells called gonadotrophs
• FSH is for ovarian follicular development, LH for gonadal steroidogenesis
• HCG is a placental hormone nearly identical to LH
• All are heterodimers that share identical α chain but distinct β chain
• Preparations are administered either subcutaneously or IM
• Half life vary from 10 – 40 hours
15. GONADOTROPINS
1. FSH analogs( Follitropin alfa)
• Mechanism of action: activates FSH receptors and mimiks endogenous FSH
• Clinical application: controlled ovarian hyperstimulation in women and treatment
hypogonadotropic hypogonadism in men Subcutaneous injection
• Toxicity: OHSS, multiplepregnancies,Gynecomastia Depression and oedema
• As above for follitropin beta, urofollitropin and menotropin
16. GONADOTROPINS
1. LH Analogs (hCG)
• Mechanism of action: agonist at LH receptors
• Clinical application:initiation of ovulation during controlled ovarian
hyperstimulation
• Administered as IM injection
• Toxicity: OHSS, multiple pregnancy, Gynecomastia in men, Headaches, Depression
and oedema
• As above for lutropin and choriogonadotropin alfa, menotropins
17. Thyroid stimulating hormone (TSH)
CLINICAL IMPORTANCE
For monitoring patients who have been treated surgically for thyroid
carcinoma by testing for recurrence through assessing TSH-stimulated whole
body Iodine 131 scans and thyroglobulin determination
18. ADRENOCORTICOTROPIN (ACTH)
• CLINICAL IMPORTANCE
For diagnosing central adrenal insufficiency (CRH/ACTH) or peripheral (cortisol
deficiency) deficiency particularly in suspected congenital adrenal hyperplasia
19. • Kindly refer to your lectures on drugs that act on the hypothalamus to look
up GNRH agonist/antagonist, Dopamine agonist/antagonist and posterior
pituitary hormones (oxytocin/vasopressin).
20. References
1. Bertram G K, Masters S B, Trevor J A, Basic and clinical Pharmacology
twelfth Edition 2012; Pg 659-681.
2. Charles C, Robert E, Modern pharmacology with clinical applications
