ANTERIOR AND POSTERIOR PITUITARY HORMONES.pptx

anterior and posterior pituitary hormone

1. ANTERIOR PITUITARY HORMONES BY DR BAKUT J.OHN MAIGANGA DEPARTMENT OF CLINICAL PHARMACOLOGY AND THERAPEUTICS FACULTY OF BASIC CLINICAL SCIENCES ABUTH, ZARIA.

2. Outline Introduction Growth hormones Gonadotropins Thyroid stimulation hormone Adrenocorticotropin Conclusion

3. 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

4. Introduction Six major hormones are secreted by the adenohypophysis or anterior pituitary gland The secretion of anterior pituitary hormones is controlled in part by hypothalamic regulatory factors that are stored in the hypothalamus and are released into the adenohypophyseal portal vasculature

5. 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

6. 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 M any 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

7. 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

8. 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

9. 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

10. 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

11. Growth Hormones 2. Mecasermin ( IGF -1 Agonist) Mechanism of action: Recombinant form of IGF -1 that 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

12. Growth Hormone (Antagonist) 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 are octreotide and Lantreotide

13. 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 : Acromegaly and several hormone-secreting 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

14. Growth Hormone (Antagonist) 2. 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

15. 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

16. GONADOTROPINS (FSH, LH, HCG) Menotropins : purified from urine of post menopausal women, FSH-like properties, LH-like substance, also called hMG (Human menopausal gonadotropin) Follicle stimulating hormone : Urofollitropin (from urine of post menopausal women), Follitropin alfa and Follitropin beta are recombinant forms with different carbohydrate side chains and shorter half life Luteinizing hormones : Lutropin alfa is administered subcutaneously and use in combination with follitropin for follicular development Human Chorionic Gonadotropin : A glycoprotein extracted and purified from urine, choriogonadotropin alfa is the recombinant form

17. GONADOTROPINS 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 , multiple pregnancies, Gynecomastia in men, Headaches, Depression and oedema As above for follitropin beta, urofollitropin and menotropins

18. GONADOTROPINS 2. 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

19. 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

20. ADRENOCORTICOTROPIN (ACTH) CLINICAL IMPORTANCE For diagnosing central adrenal insufficiency ( CRH /ACTH) or peripheral (cortisol deficiency) deficiency particularly in suspected congenital adrenal hyperplasia

21. 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).

22. References Bertram G K, Masters S B, Trevor J A, Basic and clinical Pharmacology twelfth Edition 2012; Pg 659-681. Charles C, Robert E, Modern pharmacology with clinical applications

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