Insulin & Sex Hormones Rushi.pptx

insulin & sex hormone

1. Insulin & Sex Hormones Presented by : Rushikesh S Tidake M.Pharm II sem P harmacology RSCP B uldana

2. Insulin Is a polypeptide hormones produce by ß-cells of Langerhans of pancreas . It has profound influence on metabolism of Carbohydrates ,fat & proteins. It is considered as anabolic hormone

3. It was the first hormone to be isolated purified & synthesized First hormone to be sequenced First hormone to be produced by recombinant DNA technology

4. Structure Human Insulin contain 51 amino acids arranged in two Polypeptide chains Chain A = 21AA Chain B = 30AA Two interchain Disulfide bridge = A7-B7 & A20-B19 Intrachain Disulfide link in chain A = 6-11

5. Synthesis Gene for protein synthesis is located on Chr 11 Produced from ß-cells of Langerhans of pancreas Synthesis involve two precursor - Preproinsulin = 108AA -Proinsulin = 86AA

6. These are sequentially degraded to form the active hormone Insulin and Connecting peptide (C-peptide) C-peptide has no biological activity,however its estimation in plasma serves as the useful index for endogenous production of insulin. In ß –cells , Insulin combines with zinc to form a complex & stored in granules.

7. Transport , fate and excretion : Insulin circulates in plasma partly in a protein bound form and partly free form . It is taken up mostly by liver kidney and skeletal muscle . No insulin is taken up by red blood cells and brain. It is degraded by tissues like liver , kidneys testes and placenta. It is metabolised by glutathione – insulin transhydrogenase ( insulinase ). This enzymes separates the two chains. This individual chains are degraded by proteolytic enzymes

8. Actions of insulin : Liver : In the liver , insulin increases the activity of two enzymes : 1. Glucokinase which increases glucose uptake . 2. Glycogen synthetase which increases glycogen depositon . It decreases the activity of other two enzymes : 1. Phosphorylase and CAMP , inhibition of which decreases glycogenolysis 2. Enzymes concerned with glyconeogenesis ( fresh synthesis of glucose from non – carbohydrate sources As a result ,the breakdown of liver glycogen and fresh synthesis of glucose is decreased . But glucose is mobilised to the liver and deposited as glycogen.

9. B. Adipose tissue : insulin increases the permeability , uptake and utilization of glucose in the fat cell . Increased glucose utilization leads to the synthesis of glycerol , α glycerophosphate and fatty acids . The later two compounds combine to form triglyceraids . Thus insulin induces lipogenesis but it prevents lipolysis C. Skeletal muscle : Insulin stimulate the uptake of glucose by the muscle cell . It stimulates the entry of amino acids into the cells and its incorporation into proteins (anabolic effect) But it prevents breakdown of fat in muscle ( antilpolytic effect)

10. Classsification of Preparation of Insulin : A.) Short Acting Plain insulin Insulin zinc Suspension ( humulin ) Intermediate Insulin Globin zinc insulin Isophane Insulin Long Acting Protiamine zinc Insulin Ultralente

11. B. Newer insulin : Nuso : It is bovine insulin in clear , neutral solution Actrapid : It is a clear , neutral solution of monocompetent porcine insulin Rapitard : It is a cloudy mixture of actracid and bovine insulin Monotard : It contains highly purified porcine insulin . It is antigenic. Human Insulin : They are obtained by recombinant DNA technology from E.coli or yeast .They are widely used at present. Advantages : More water Soluble Rapid S.C absorption Useful in insulin resistance Useful in allergy to commercial isolations Useful for short term use in surgery or infection

12. Oral Antidiabetic Drugs Insulin is ineffective orally and so it has to be injected . But the oral antidaibetic drugs lower blood glucose level on oral administration. Classification of drugs Sulfonylureas a) First generation Tolbutamide Chlorpropamide b) Second generation Glibenclamide Glipizide Glyclazide Glymepridie 2. Bigunaides Metformin

13. Sulfonylureas MOA: Stimulation of the synthesis and release of insulin from β cells of islets of langerhans Increase the number of beta cells Inhibition of glygenolysis and glyconeogenesis Decrease the rate of insulin degradation . Absorption , fate and excretion: Sulfonylureas are rapidly absorbed from GIT. They are partly bound to plasma proteins. They are metabolised in liver and excreted in urine.

14. Biguanides : MOA The presence of exogenous or endogenous insulin is necessary for action of biguanides , but insulin release from pancreas is not stimulated Peripheral utilization of glucose is stimulated Absorption of glucose from intestine is inhibited . Absorption, fate and excretion : These are well absorbed from GIT. Maximum activity occures in 4 Hrs. They are eliminated through urine within 24 Hrs

15. Sex hormones : Sex Hormones belongs to steroid class of compound and are produced in gonads. i.e testes in male and ovaries in female . Their activity is controlled and monitored by the anterior lobe of pituitary glands. Perhaps because of this inherent characteristics the sex hormones are invariably termed as secondary sex hormones and the hormones of anterior lobes of pituitary glands are called as primary sex hormones.

16. Classification Androgens : testosterone Estrogens : Estrone , Estradiol Gestogens : Progesterone

17. Testosterone Mode of action : Androgen binds to the specific nuclear receptor in target cell. Although the testosterone itself is the active ligand in muscle and liver , in other tissues it must be metabolized to the derivatives such as DHT e.g. After diffusing into the cells of the prostrate , seminal vesicles , epidermis and skin , testosterone is converted by 5 α - reductase to DHT , which binds to the receptor .

18. Actions: Sex organs and secondary sex characters : Testosterone is responsible for the all changes that occurs in boy during puberty. Growth of genitals , growth of hairs , larynx grows and voice deepens . 2. Testes : moderately large doses cause testicular atrophy by inhibiting Gn secretion from pituitary . Still larger doses have direct sustaining effect and atrophy is less mark ed . 3. Skeleton and skeletal muscles ( Anabolics ) : Testosterone is responsible for pubertal spurt of growth in boys and to a smaller extent in girls . There is rapid bone growth, both in thickness as well as length . After puberty the epiphysis fuse and linear growth comes to halt.

19. Uses : Testicular failure : It may be primary – in children , resulting in delayed puberty . Secondary testicular failure occur mainly as loss of libido , muscle mass , feminisation , impotency . These are corrected gradually over months. Hypopituitarism : Hypogonadism is one of the feature of hypopituitarism . AIDS related muscle wasting : Testosterone therapy has been shown to improve weakness and muscle wasting in AIDS patient with low testosterone level . Hereditary angioneurotic edema : This is a genetic disorder . The attack can be prevented by 17 α alkylated androgens but not by testosterone . Ageing : Because testosterone level decline in old age , it has been administered to elderly mails to improve bone mineralisation and muscle mass.

20. Estrogen (Female Sex hormones ) Mechanism of Action Genomic Actions : Binds to specific receptors ( er ) Conformational changes ( receptor dimerization leading to interaction with estrogen response Element , ERE , of target genes ) regulates the protein synthesis. Nongenomic Actions : - Ers located on the cell membrane

21. Actions : Sex organs : The estrogens bring about pubertal changes in the female including of uterus , fallopian tubes and vagina . Vaginal epithelium gets thickened , stratified and cornified . 2. Secondary sex characters : Estrogen produce at puberty cause growth of breasts –proliferation of ducts & stroma , accumulation of fats.The pubic and axillary hair appear, feminine body contours and behaviour are influenced. 3. Metabolic effects : Estrogen are anabolic , similar to but weaker than testosterone . Therefore small amount of estrogen may be contributing to the pubertal growth spurt even in boys.

22. Uses : 1.)Primary Hypogonadism : In estrogen deficinet patients Treartment usually begins at 11 -13 yrs of age To mimic the physiology of puberty Start with small dose of estrogen on days 1-21 each month and increase to adult doses untill menopause Preogestin therapy simulataneously 2.) Hormone replacement therapy : Highly efficacious in suppresing the peri - menopausal syndromes Dose of estrogen used is less Conjugated estrogens is 0.625mg/day Progestin should be added for 10-12days each month. Recent findings emphasis a number of risks and limitations

23. Progesterone Mode of action : The progesterone receptors has limited distributio in the body confined mainly to the feamle genital tract , breast , CNS , pituitary . Upon Hormone binding PR undergoes dimerization , attaches progesterone response element (PRE) of target genes and regulates transcription through co-activators

24. Actions : Uterus : Progesterone brings about secretory changes in the estrogen primed endometrium : hyperemia , tortuocity of glands and increased secretion occurs while epithelial proliferatiom is halted it is lack of progestinal support which causes mucosal shading during menstruation . Cervix : Progesterone converts the watery cervical secretion induced by estrogens to viscid sacnty and cellular secretion which is hostile to sperm pentration . Vagina : Progesterone induces pregnancy like changes in the vaginal mucosa : leucocyte infiltation of cornified epithelium occurs Breast : Progesterone causes proliferation of acini in the mammary glands CNS : High circulating concentration of progesterone appears to have seadtive effect.It can also affect mood

25. Uses : 1.) As contraceptive : Most common use. 2.)Hormone Replacement Therapy : Used in the nonhysterectomised post menopausal woman estrogen therapy is supplemented with a progestin for 10-12 days each month to reduce risk of endometrial carcinoma . 3.) Dysfunctional Uterine bleeding : Progestin enlarge those promptly stops the bleeding and keeps it abeyance as long as therapy is given . Cyclic treatment regularises and normalises menstrual flow. 4.) Endometrial Carcinoma : Progestin are palliative in about 50% cases of advanced or metastatic endometrial carcinoma .High doses are needed.

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