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In The Name of Almighty Allah 1 MALE SEX HORMONES OH OH H H H H O H H O H TESTOSTERONE DIHYDROTESTOSTERONE Natural androgens ANDROGENS • Prototype is testosterone • Main function: Development and maintenance of primary and secondary sex characteristics in males (androgenic) • protein retention (anabolic action) ANDROGENS The male sex hormones or androgens are produced by Leydig cells of testes in response to LH and to a minor extent by adrenal glands in both the sexes. Ovaries also produce a small amount of androgens. Biosynthesis of androgens: Site: synthesized in the interstitial tissue by the leydig cells. Precursor: Cholesterol It is first converted to pregnenolone by cytochrome p450 side chain cleavage enzyme which then forms androstenedione by two pathways: 1. Through progesterone (Progesterone (or ∆4) pathway) 2. Through 17-hydroxypregnenolone.(Dehydroepiandrosterone or ∆5 pathway) 4 Dehydroepiandrosterone (or ∆5) pathway, Progesterone (or ∆4) pathway 6 The conversion of pregnenolone to testosterone requires the action of five enzyme activities contained in three proteins: (1) 3β-hydroxysteroid dehydrogenase (3β-HSD) and ∆5,4-isomerase; (2) 17α-hydroxylase and C17-20 Lyase and (3) 17β-hydroxysteroid dehydrogenase (17β-OHSD). The ∆5 route appears to be most used in human testes. Regulation: The production of androgens is under the control of LH and FSH. Regulated by negative feedback mechanism The rate limiting step is the delivery of cholesterol to IMM by StAR. Steroidogenic acute regulatory protein (StAR) 7 Testosterone is metabolized by two pathways. First pathway involves oxidation at the 17 position, occurs in many tissues, including liver and produces 17-ketosteroids that are generally inactive or less active than the parent compound. Second pathway (Dihydrotestosterone Is Formed From Testosterone in Peripheral tissues) occurs primarily in target tissues involves reduction of the A ring double bond and the 3 Ketosterone, a reaction catalyzed by the NADPH-dependent 5 α reductase 5 mg of testosterone is produced daily by testes. Approximately 400 µg of DHT is produced daily Some estradiol is formed from the peripheral aromatization of testosterone. 8 Transport of androgens: In the plasma testosterone and DHT bind to two proteins1. Sex hormone binding globulin ( SHBG) binds 97 to 99% and 2. Testosterone-estrogen binding globulin( TEBG). A small fraction is in free form. Both these proteins are synthesized in liver. The plasma testosterone level in normal men is about 0.7 µg/dl while in women it is < 0.1 µg/dl. Mode of action: Group I hormone Both testosterone and dihydrotestosterone bind to a single class of receptors on the target tissues. The affinity of DHT for the receptor is much higher compared to testosterone. Receptor sites for androgens are found in muscle, brain, and other target tissues. 9 Physiological and biochemical functions of androgen: The androgens influence 1. Growth, development and maintenance of male reproductive organs. 2. Sexual differentiation and secondary sexual characteristics. 3. Spermatogenesis. 4. Male pattern of aggressive behavior. 5. pubertal transformation: • • • • • • • • Enlargement of testes, penis and scrotum Pubic and axillary hair Bone growth Red cell mass increase Skeletal muscle mass increase Larynx enlarges - deepening of the voice Increase in sebaceous glands - often cause of acne Development of Beard 10 Biochemical functions: Protein retention ( Anabolic action) Effect on protein metabolism: Androgens promote RNA synthesis( transcription) Protein synthesis( translation). Rapidgrowth of musculo-skeletal system associated with puberty. Effect on carbohydrate and fat metabolism Glycolysis, Production of D-fructose from D-glucose by seminal vesicles. fatty acid synthesis and citric acid cycle. Effects on mineral metabolismAndrogens promote Mineral deposition and bone growth Kidney reabsorption of Na+, Cl- and water. 11 Abnormalities associated with male sex hormones: Hypogonadisn is a disorder characterized by a defect in testosterone synthesis. It may be of two types. 1. Primary hypogonadism is caused by a failure of testes to produce testosterone. 2. Secondary hypogonadism is due to an impairment in the release of gonadotropins. 12 All Praise be to HIM, The Lord of the Universe,The Lord of the day of Judgment Thanks a lot 13 14