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Significance of DHT

Significance of DHT. Androgen receptor has a higher affinity for DHT Can get effects with low levels of circulating testosterone Secondary sex characteristic tissue in the male expresses 5 a -reductase . External Genitalia Differentiation. Dihydrotestosterone. Development of penis

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Significance of DHT

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  1. Significance of DHT • Androgen receptor has a higher affinity for DHT • Can get effects with low levels of circulating testosterone • Secondary sex characteristic tissue in the male expresses 5a-reductase

  2. External Genitalia Differentiation

  3. Dihydrotestosterone Development of penis scrotum and accessory sex glands Testis Determining Factor (SRY gene product) No TDF XX Female XY Male Testes develop Ovaries Develop No Testosterone No AMH Sertoli cells secrete anti-mullerian hormone (AMH) AMH causes leydig cells to differentiate Degeneration of Mullerian duct Degeneration of Wolffian duct Mullerian ducts become the oviducts, uterus, cervix and part of the vagina Testosterone Development of male duct system

  4. Brain or Behavioral Sex

  5. Brain and Behavioral Sex Differentiation Genetics Gonadal Steroid Hormones Sexual Behavior Brain Structure Experience

  6. Brain Sexual Differentiation • Rat female • Give testosterone shortly after birth • fail to copulate or cycle like female as adult • Sexually dimorphic nucleus • Human male and female differences in behaviors • aggression • childhood play • 3D visual rotation

  7. Descent of the Testis into the Scrotum

  8. Testicular Descent Fusion of the tunica albuginea and peritoneum to form the visceral tunica vaginalis

  9. Spermatic Artery Front View Fusion of Peritoneum and Gubernaculum Testis Gubernaculum Peritoneum Inguinal Ring

  10. Rapid growth of gubernaculum Spermatic Artery Peritoneum Visceral Growth Visceral Growth Inguinal Ring Testis Peritoneum Gubernaculum (rapid growth) Parietal Tunica Vaginalis Testis is pulled down to the inguinal ring. Visceral Tunica Vaginalis

  11. Gubernaculum regresses Spermatic Artery Peritoneum Visceral Growth Visceral Growth Inguinal Canal Peritoneum Testis Vaginal Process Gubernaculum (Regressing) Parietal Tunica Vaginalis Testis pulled into scrotum Visceral Tunica Vaginalis

  12. Spermatic Artery Continued regression of Gubernaculum Peritoneum Inguinal Canal Testis pulled deeper into Scrotum Peritoneum Vaginal Process attaches to Scrotum VaginalProcess Testis Space between Visceral and Parietal T.V. is continuous with Peritoneum Parietal Tunica Vaginalis Visceral Tunica Vaginalis Gubernaculum (Fully Regressed)

  13. Failure or Problems With Testicular Descent • Cryptorchid - highly heritable • Unilateral or bilateral • Germ cells fail to multiply and then die, sertoli cells only in seminferous tubules • High percentage develop testicular cancer • Surgical correction possible but does not reduce cancer risk

  14. Normal Dog Seminiferous Tubule

  15. Cryptorchid Dog Seminiferous Tubule SertoliCells

  16. Failure or Problems With Testicular Descent • Inguinal Hernia • Cryptorchid - highly heritable • Unilateral or bilateral • Germ cells fail to multiply and then die, sertoli cells only in seminferous tubules • High percentage develop testicular cancer • Surgical correction possible but does not reduce cancer risk

  17. Inguinal Hernia Loop of Intestine

  18. Abnormalities in Development

  19. The Freemartin in Cattle • Female born twin to a bull • Placenta membranes of the 2 fetuses fuse • Common blood supply • At time of testis formation • Before ovarian formation • Both fetuses share a common hormone milieu • testosterone • anti-mullerian hormone • Animals are chimeric (WBC from other twin) • TDF (SRY) expressed in both individuals

  20. Normal

  21. Freemartin

  22. Normal Vs. Freemartin

  23. Freemartin • AMH from bull - blocks Mullerian ducts • Posterior vagina, no anterior vagina • Testosterone from bull • clitoral enlargment • Brain changes like that of male • Ovaries do not grow but are chimeric • Ovotestis • SRY and therefore AMH and Testosterone • Further changes and adult male behavior • Use as estrus detector • Abnormalities exist as a continuum

  24. Testicular Feminization in an XY Individual • No androgen receptor • Testis • No testosterone response so no Wolffian duct development • AMH present so mullerian ducts regress • External genitalia is female due to lack of androgen

  25. Testicular Feminization

  26. 5 Reductase Deficiency in an XY Individual • Guevedoces (penis at 12) • Testis • AMH present so Mullerian ducts regress • Wolffian ducts • psuedovagina and female external genitalia • at puberty may differentiate into more of a phenotypic male

  27. Guevedoces Development Normal tissue dependent upon testosterone is shown in black.

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