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Gonad Hormones : Male

Gonad Hormones : Male. Prof.Dr .Gülden Burçak 2011-2012. Testis male sex hormones male germ cells. Testis : two functional units. Semineferous tubules lined with Sertoli cells and germ cells (spermatogonia) for production and transport of sperm .

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Gonad Hormones : Male

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  1. Gonad Hormones : Male Prof.Dr.Gülden Burçak 2011-2012

  2. Testis malesexhormones malegermcells

  3. Testis : two functional units • Semineferous tubules lined with Sertoli cells and germ cells (spermatogonia) for production and transport of sperm . Sertoli cells provide the environment necessary for germ cell differentiation and maturation • Interstitial cells ( Leydig cells) for production of testosterone.

  4. Hypothalamic-Pituitary-Testis Axis • Constant pulsatile release of GnRH from the hypothalamus • Synthesis, storage and secretion of gonadotropins (FSH and LH) from the anterior pituitary • (-)feedback relationship between the androgens and GnRH, FSH, LH secretions • Prolonged exposure to LH results in desensitization

  5. In childhood • testosterone and plasma gonadotropin levels are low • HPA is highly sensitive to (-) feedback effects of gonadal steroids • Onset of puberty • Bursts of GnRH release • Sleep associated surges in LH secretion and to a lesser extent in FSH secretion • Later in puberty pulsatile gonadotropin secretion throughout the day and night and more sustained plasma gonadotropin, testosterone and dihydrotestosterone

  6. For normal testicular function, GnRH pulses occur at a frequency of 3.8 pulses every 6 hours. • At a lower pulse rate FSH release ; at a higher pulse rate LH is more prominent • Circulating half-life : FSH,4 hours ; LH, 30 minutes • Testosterone : diurnal rythmic pattern, highest in the early morning

  7. LH • binds Leydig cells • testosterone synthesis and secretion • secretion is inhibited by both testosterone and estradiol • conversion of testosterone to estradiol in brain, pituitary and testes • FSH • binds Sertoli cells • synthesis of androgen binding protein, aromatase enzyme complex, inhibin • secretion is primarily inhibited by inhibin B but also by testosterone

  8. Testosterone biosynthesis • Cholesterol • de novosynthesisorfrom LDL • cholesterolestersstorage in cytoplasm • LH (cAMP) (acute) : esteraseactivationandcholesterol transport totheinnermitochondrialmembrane (steroidogenicacuteregulatory protein (StAR) • LH (cAMP) (chronic) : steroidogenicenzymesynthesis

  9. Side chain cleavage and removal of the six-carbon fragment • Cytochrome P450 side chain cleavage • Two hydroxylations first at C22 then at C20 (O2 and NADPH) • Cholesterol 20,22- desmolase

  10. 5α-reductase,type I : liver Type II : reproductive tissues and peripheral targets

  11. Daily testicular production • 5mg testosteron, • 50-100μg DHT ; %25 of DHT in circulation • %25 of estradiol (E2) in circulation • Testosterone : a circulating precursor of DHT and E2 • DHT (5α-reductase) in liver, kidney, muscle, prostate, external genitalia and genital skin • E2 (aromatase enzyme complex) in muscle, liver, kidney, brain, adipose tissue.

  12. 50% loosely bound to albumin (> 400 mg /L) • 45% bound with high affinity to SHBG • 1-2% to CBG • < % 4 is free • The normal level of SHBG is about 30-50% lower in men than in women • SHBG levels may be elevated in testosterone deficient men. • A change in the level of SHBG causes a greater change in the free testosterone level than in the free estradiol level.

  13. Effects of androgens • Sexual differentiation • Spermatogenesis • Development of secondary sexual organs • Anabolic metabolism and gene regulation • Male pattern behaviour • Estradiol : sexual behavior and control of LH secretion

  14. Targets for testosterone • Embryonic Wolffian structures, spermatogonia, muscles,bone, kidney and brain • Targets for dihydrotestosterone • Prostate, external genitalia and the genital skin • The kidney is a major target tissue of the androgens : general enlargement of the kidney

  15. Excretory metabolites : inactive or less active • Oxidation at the 17-position in many tissues, including the liver • 17 ketosteroids : androsterone and etiocholanolone • conjugated with glucuronide and sulfate • Androstanediol

  16. Pathological States • Primary hypogonadism • Genetic disorders : Klinefelter’s syndrome • Androgen receptor defects : Testicular feminization syndrome • Inherited enzyme defects : 20,22-desmolase, 3ß-hydroxydehydrogenase,17α-hydroxylase 17,20 desmolase , 17-ketosteroid reductase • Failure of the pituitary/hypothalamus to respond to low testosterone levels

  17. Inhypogonadism • Hypothalamus : LowGnRH ; low FSH,LH; low E2 /testosterone • Pituitary : HighGnRH ; low FSH,LH ; low E2 /testosterone • Gonad : HighGnRH ; high FSH,LH ; low E2 /testosterone • Hyperprolactinemia is associatedwithdiminished libido andimpotence

  18. Hypergonadism • Testicular hyperfunction : Testicular tumors (often produce hCG and α-fetoprotein) • Hypothalamic/pituitary hyperactivity usually from a tumor

  19. Benign prostatic hypertrophy : extensive and uncontrolled division of prostate cells • Testosterone / dihydrotestosterone + estradiol • Erectile dysfunction may occur secondarily to vascular problems associated with diabetes, atherosclerosis • Infertility

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