1. ENDOCRINE 12/11/20111Dr.tarig hussein

2. Hormones:- Hormones are chemical substances that are synthesized and secreted by ductless glands, released directly to blood in response to target tissue. Classification:- Group I “Lipophilic” Lipid sol. Group II “Hydrophilic” water sol. 12/11/20112Dr.tarig hussein

3. Group IGroup II 1- SolubilityLipophilicHydrophilic 2- typeSteroids lodothyromines T3 T4 Polypeptides proteins glycoproteins catecholamines 3- Transport proteinsYesNo 4- Plasma half lifeLong “Hours-days”Short “min” 5- ReceptorIntracellularPlasma membrane 6- MediatorReceptor-hormone complexcAMP, Ca, metabolites of complex phosphoinos-itides & others 12/11/20113Dr.tarig hussein

4. Classification according to chemical nature:- 1- Amino acids & A.A derivative include catecholamines & thyroid hormone. 2- Protein & polypeptide (3 A.A. – 200 A.A.). 3- Steroid hormone. 12/11/20114Dr.tarig hussein

5. Classification of hormones by mechanism of action:- I- Hormones that bind to intracellular receptors: Androgens. Calcitriol (1.25[OH] 2 –D 3 ). Estrogens. Glucocorticoids. Mineralocorticoids. Thyroid hormones (T 3 and T 4 ) II. Hormones that bind to cell surface receptors: A.The second messenger is cAMP: α 2 -Adrenergic catecholamines. β-Adrenergic catecholamines. 12/11/20115Dr.tarig hussein

6. Adrenocorticotrpic hormones. Antidiuretic hormones. Calcitonin, FSH, LH, Glucagon, somatostatin and TSH. B. The second messenger is cGMP: Atrial natriuretic factor. Nitric oxide. C. The second messenger is calcium or phosphatidyl inositols or both: α 1 -Adrenergic catecholamines. Angiotensin II. Cholecystokinin. Gastrin, oxytocin. D. The second messenger is a kinase or phosphatase cascade: Erythropoietin. Growth hormones. Insulin prolactin. 12/11/20116Dr.tarig hussein

7. Mechanism of hormone action and cell signaling:- Most hormones bind to cell surface receptors and trigger cascades of enzymatic reaction. We well be focus on four general mechanisms: 1- The adenylate cyclase cascade, leading to an increased level of cyclic AMP and the activation of a protein kinase, is a major transduction pathway. 2- the phosphoinos-itides cascade is another generally used pathway of hormone action : the hydrolysis of a membrance phospholipid produces two intracellular messengers inositol trisphosphate opens calcium channels, and diacylglycerol activates a protein kinase. 12/11/20117Dr.tarig hussein

8. 3- Insulin and many growth factors act by stimulating the tyrosine kinase activity of their receptors. Moreover, several oncogene products have tyrosine kinase activity or trigger this cascade. 4- steroid and thyroid hormones act quite differently cAMP is a second messenger in the action of many hormones. The essential features of this concept are 1- The plasma membrane contains receptors for hormone 2- The combination of a hormone with its specific receptor leads to the activation of adenylate cyclase 3- The increased activity of adenylate cyclase increases the level of cAMP in the cytosol 4-cAMP then acts inside the cell to alter the rate of one or more processes. An important feature of the second messenger model is that the hormone need not enter the cell 12/11/20118Dr.tarig hussein

9. Adenylat cyclase activated by G- Protein Alfred Gilman has shown that the G- protein is a peripheral membrane protein consisting of α(45 kd), β (35 kd), and Ύ (7 kd) subunits. It interconvert's between a GDP form and a GTP form. The GTP form activates adenylate cyclase, whereas the GDP form does not. The rate of GTP-GDP exchange in the absence of hormone is very low because the uncatalyzed reaction has a very large activation barrier. 12/11/20119Dr.tarig hussein

10. cAMP activates protein kinase by dissociation the 2catalytic subunits from 2regulatory subunits. The adnylate cyclase cascade greatly amplifies such weak hormone signals. Three steps in the cascade provide a high degree of amplification: 1- Each hormone-receptor complex catalyzes the formation of many Gα-GPT. 2- Many molecules of cAMP are formed by an activated adenylate cyclase. 3- Each cAMP-activated protein kinase can alter the activity of many molecules of each target protein. 12/11/201110Dr.tarig hussein

11. Cholera toxin stimulates adenylate cyclase by inhibiting the GTPase activity of Gs( prevent the capacity to hydrolyze bound GTP to GDP) and the G- protein is looked in the active form. Hence adenylate cyclase become activated in the absence of hormone and the level of cAMP becomes abnormally high, which stimulates the active transport of ions and leads to a very large efflux of Na+ and water into the gut. Theophylline and caffeine inhibit the phosphodiesterase enzyme and use cAMP as second messenger 12/11/201111Dr.tarig hussein

12. RECEPTOR TRIGGERED HYDROLYSIS OF PHOSPHATIDYL INOSITOL BISPHOSPHATE GENERATES TWO MESSENGERS:- The binding of a hormone such as serotonin to a cell surface receptor leads to the activation of phosphoinositidase (also called phospholipase C). This membrane bound enzyme hydrolyzes the phosphodiester bond linking the phosphorylated inositol unit to the acylated glycerol moiety. Two messengers inositol (IP 3 ) and diacylglycerol are formed by the cleavage of PIP 2. 12/11/201112Dr.tarig hussein

13. IP 3 releases calcium ion into the cytosol and diacylglycerol activates protein kinase. Eicosanoid hormones are derived from polyunsaturated fatty acids. 12/11/201113Dr.tarig hussein