Anterior pituitory hormones and analogues

Pituitory gland, its type and hormones secreted from anterior lobe their analogues

1. BY:- shubham kumar vishwakarma B.Pharm V semester Anterior Pituitary Hormones

2. Introduction The ENDOCRINE SYSTEM includes all the glands (ductless glands) of the body and the hormones produced by those glands – maintain homeostasis Hormone (Greek hormaein—to stir up) is a substance of intense biological activity that is produced by specific cells in the body and is transported through circulation to act on its target cells. Hormones are secreted by the endocrine or ductless glands.

3. The Anterior pituitary hormones

4. Classification 1.Somatotropic Hormones 1- Growth Hormone (GH) 2- Prolactin (Prl) 2.Glycoprotein Hormones 1- Luteinizing Hormone (LH) 2- Follicle-Stimulating Hormone (FSH) 3- Thyroid-Stimulating Hormone (TSH)

5. Classification 3. derived Hormones 1- Corticotropin: ACTH 2- Melanocyte-Stimulating Hormones: a-MSH, b-MSH 3- Lipotropins: b-LPH, g-LPH

6. 1. Growth Hormone (GH) Structure:- Receptors are JAK-STAT protein kinase type Regulation: Hypothalamus - secretes GHRH and also inhibitory GHIH (Somatostatin – also in pancreas) – controls secretion (increasing or decreasing cAMP) - all are GPCR GH secretion – high in children, reaches maximum level in adolescent and decreases in age related manner - Occurs in irregular pulse, falls between these pulses Amplitude of secretory pulses is maximum at night, shortly after onset of deep sleep

7. Regulation Stimulation: By GHRH(Somatorelin) Inhibition: By Somatostatin Other Factors stimulating release Hypoglycemia, Exercise,Stress,Ghrelin Other Factors inhibiting release Free fatty acid ,Corticosteroid, Hyperglycemia

8. Regulation

9. Physiological Role Promotes Growth - Coordinated action of several hormones GH promotes growth of all organs by inducing hyperplasia –proportionate increase in the size and mass of all parts – except brain and eye – Retention of Nitrogen and other tissue constituents – more protoplasm formation – Positive Nitrogen balance – due to increase uptake of amino acids – Promotes utilization of fats – spares glucose (muscles)

10. Physiological Role Direct Effects Stimulation of Lipolysis Stimulation of Hepatic glucose output Production of Insulin-like growth factors Catabolic effects in lipid cells and anabolic effects muscle Mixed effects on carbohydrate metabolism Increase Protein synthesis

11. Physiological Role Indirect Effects Mediated by IGF-1 (Somatomedins) Increase cell numbers Positive Nitrogen balance Increase Protein synthesis

12. M.O.A Via JAK/STAT Cytokine receptor super family Induce conformational change Recruitment and activation of JAK kinase Phosphorylation Dimerization Nuclear translocation

13. M.O.A

14. Disease Conditions Related to GH Hyposecretion Dwarfism(Pituitary) Hyper secretion Gigantism in children Acromegaly in adult

15. Uses Childhood pituitary dwarfism Dose-25mcg/kg/day SC or IM Idiopathic short stature Other uses TS, PS, NS, SGA,CRF- Growth Wasting in HIV patient- ↑ Lean body mass ,weight Short bowel syndrome- Improve GI function Wound healing in large born Athlete-Dope drug

16. Adverse effect Childrens:- Nausea,Vomiting,↑ICP,Scoliosis Adults:- Peripheral edema,Arthrlgia,Myalgia Carpal tunnel syndrome Otitis media, Proliferative retinopathy

17. GH inhibitor Somatostatin • Somatostatin:14 amino acid peptide • Produce mainly by hypothalamus and also in GIT • Inhibits secretion of GH, TSH and prolactin by pituitary and insulin and glucagon by pancreas and all GIT secretions (Gastrin, HCl) • All GIT secretions are inhibited including HCl - Diarrhoea, stetorrhoea, hypochlorhydria, nausea, dyspepsia etc. occurs • Constrict hepatic, splanchnic and renal blood vessels • Uses: – Acromegaly: limited use due to short half-life (2-3 min) – GI haemorrhages (250 mcg slow IV, 3 mg infusion for 12 Hrs) – Pancreatic, biliary and intestinal fistulae – antisecretory effects – APUD tumours producing excess HCl – Diabetic ketoacidosis (inhibits glucagon and GH secretion) • Drawbacks: Short duration (2-3 min) and rebound GH secretion

18. GH inhibitor Octreotide • Synthetic analogue of Somatostatin and 40 times more potent • Longer duration of action (t1/2 – 90 min) • In acromegaly preferred - Injection octreotide (100 μg) s.c thrice daily • Monitor serum GH and IGF-1 levels to assess effectiveness • Goal – decrease GH levels < 2ng/ml & IGF-1 levels within normal range for age and sex • Octreotide binds preferentially to receptors on GH secreting tumors - decreases tumor size • Octreotide inhibits TSH secretion and is treatment of choice in thyrotrope adenoma that over secrete TSH and not good candidate for surgery

19. GH inhibitor • Adverse effects: abdominal pain, steatorrhoea, diarrhoea and gall stones

20. Prolactin Secreted by Lactotrophs of the Anterior Pituitary Single polypeptide chain composed of 199 AA Secretion Starts early in the fetal stage Decline shortly after birth and remain low in male In female increase with pregnancy Maximum at parturition

21. Prolactin Regulation Inhibited by Dopamine Stimulated by TRH,VIP,PRP Physiological Effects Proliferation and differentiation of mammary tissue Initiation of lactation

22. Prolactin

23. Hyperprolactinemia Causes Pituitary microadenoma Dopamine antagonists Hypothyroidism associated with high level of TRH Hypothalamus or Anterior Pituitary disorders Renal failure Symptoms In females: Galactorrhea, Amenorrhea, Infertility In males: Loss of libido, Impotence, Infertility

24. Treatment Dopamine agonists Bromocriptine 1.25mg after evening meal Cabergoline, Quinagolide Other Uses Parkinsonism Acromegaly Hepatic coma

25. Gonadotropins Luteinizing Hormone (LH) Follicle-Stimulating Hormone (FSH) Human Chorionic Gonadotropin (HCG)

26. Gonadotropins Secretion LH and FSH - Gonadotrophs of the Anterior Pituitary HCG - Placenta Regulation Stimulation Gonadotropin-Releasing Hormone (GnRH) Inhibition Feed back mechanism by sex hormone CG produced by placenta after fertilization

27. Regulation of gonadotropin secretion

28. Physiological role Males LH (ICSH) Stimulate production of androgens by Leydig cells FSH Enhance sperm production by Sertoli cells Regulate spermatogenesis Females LH Induce Ovulation and stimulate Progesterone production Maintenance of corpus luteum Stimulate synthesis of testosterone and androstenedione FSH Enhance production of Estrogen Development of follicles and ovum

29. preparation Commercially availble Menotropins or hMG( human menopausal gonadotropin) 1st comercial gonadotropin product Contain FSH like and LH like substance Extracted from urine of post menopausal women FSH (purified) Urofillitropin uFSH rFSH---follitropin alfa follitropin beta HCG extracted from urine rHCG

30. uses Diagnostic Diagnosis of Pregnancy: HCG in Urine or Blood Prediction of Ovulation: LH 36 hr before Ovulation Ovustick - Immunoassay dipstick test Reproductive system disorder in males and females

31. Gonadotropin Releasing Hormone Structure Polypeptide composed of 10 amino acid residues Secretion Hypothalamic neurons with onset of puberty Pulsatile GnRH secretion Stimulates gonadotropin secretion Non Pulsatile GnRH secretion Inhibits gonadotropin secretion Gonadotropin Releasing Hormone Gonadorelin Acetate salt of synthetic human GnRH Administered SC/IM T1/2- 4 min. Synthetic analogs/GnRH analogue Goserelin (SC/IM/ Nasal spray) Histrelin,Nafarelin,Triptorelin,Leuprolide T1/2 -3 hrs

32. uses Due to stimulation 1.Female infertility Very rarely used 2.Male infertility 3-6 months of treatment is required 3.Diagnostic of LH responsiveness Side effects Female Headache, Nausea, Flushing,Local swelling Hyersensitivity dermatitis

33. Side effects In Male Hot flush ,Sweating, Edema Gynecomastia. Decreased libido Asthenia, bone density, decreased hematocrit

34. GNRH Antagonist Ganirelix. Abarelix, Cetrorelix, Degarelix Uses 1.Controlled ovarian stimulation To prevent LH surge 2. Advance prostate cancer S/E Nausea, headache Abarelix-Allergy,hypotension,QT prolongation

35. Adrenocorticotropic Hormone (ACTH) Regulation of release CRH Secretion stimulated by stress ,Hypoglycemia Circadian pattern of release Highest levels of cortisol are in early morning Depends on sleep-wake cycle Jet-lag can result in alteration of pattern Action is through MCR (GPCR) Mostly MC2R Acts on adrenal cortex • Stimulates growth of cortex (tropic action) • Stimulates steroid hormone synthesis

36. Acts on adrenal cortex • Stimulates growth of cortex (tropic action) • Stimulates steroid hormone synthesis Excess production Cushing’s syndrome/Cushing’s disease Deficiency Pituitary insufficiency

37. Regulation of ACTH

38. Cosyntropin Synthetic Human ACTH Uses I.Therapeutic uses of ACTH Very rarely use Less predictable, less consistent than corticosteroid Some time use for multiple sclerosis II.Diagnostic uses Testing integrity of HPA axis A/E Hyperandrogenism Na retention,Hypokalemia

39. Thyroid Stimulating Hormone Stimulate thyroid glands - Secrete T3 and T4 Induce hypertrophy and hyperplasia of thyroid follicles Promote iodide trapping Promote organification of and incorporation of iodine Uses Thyrotropin has no therapeutic use To stimulate I 131 uptake in tumor cells A/E Nausea,Headache,Asthenia,Neurologic abnormalities

40. Feedback control of thyroid function