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ANTERIOR AND POSTERIOR PITUITARY HORMONES.pptx
- 1. ANTERIOR PITUITARY HORMONES BY DR BAKUTJ.OHN MAIGANGA DEPARTMENT OF CLINICAL PHARMACOLOGY AND THERAPEUTICS FACULTY OF BASIC CLINICAL SCIENCES ABUTH, ZARIA.
- 2. Outline • Introduction • Growthhormones • Gonadotropins • Thyroid stimulation hormone • Adrenocorticotropin • Conclusion
- 3. Introduction • The controlof 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 majorhormones 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 inthe 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
- 7. Growth Hormones • Aprotein 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
- 8. Growth Hormone • Serumlevels 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
- 9. Growth Hormones • Inthe 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
- 10. 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
- 11. Growth Hormones • Chronicrenal 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
- 12. 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
- 13. 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 are octreotide and Lantreotide
- 14. 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
- 15. 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
- 16. 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
- 17. GONADOTROPINS (FSH, LH,HCG) A. Menotropins: purified from urine of post menopausal women, FSH-like properties, LH-like substance, also called hMG (Human menopausal gonadotropin) B. 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 C. Luteinizing hormones: Lutropin alfa is administered subcutaneously and use in combination with follitropin for follicular development D. Human Chorionic Gonadotropin: A glycoprotein extracted and purified from urine, choriogonadotropin alfa is the recombinant form
- 18. 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, multiple pregnancies, Gynecomastia in men, Headaches, Depression and oedema • As above for follitropin beta, urofollitropin and menotropins
- 19. 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
- 20. 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
- 21. ADRENOCORTICOTROPIN (ACTH) • CLINICALIMPORTANCE For diagnosing central adrenal insufficiency (CRH/ACTH) or peripheral (cortisol deficiency) deficiency particularly in suspected congenital adrenal hyperplasia
- 22. • Kindly referto your lectures on drugs that act on the hypothalamus to look up GNRH agonist/antagonist, Dopamine agonist/antagonist and posterior pituitary hormones (oxytocin/vasopressin).
- 23. References 1. Bertram GK, 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