Male Reproduction Flashcards
Androgen synthesis occurs in what cells?
Spermatogenesis occurs in what cells?
- androgen synthesis occurs in the Leydig cells
* spermatogenesis takes place in the seminiferous tubules.
Where are Leydig cells located? How does T leave the Leydig cells?
- In the interstitial tissues of the testis that reside in loose connective tissue
- testosterone diffuses either into the peritubular lymphatics surrounding the seminiferous tubules or into the capillaries and general circulation.
What is the concentration of T in the testes vs general circulation?
• The concentration of testosterone in the testis is approximately 100 times that in the peripheral circulation.
How much plasma T is bound to proteins? How much is “free”? What proteins is T bound to?
- 97% of testosterone is bound to proteins in the blood and 2- 3% is physiologically active”free testosterone”
- Approximately 44% of circulating testosterone is bound with high affinity to testosterone-estradiol-binding globulin (TeBG), the remainder is bound to albumin and other plasma proteins.
How is TeBG regulated? What is its significance during pregnancy?
• The synthesis of TeBG is stimulated by estradiol (the level in plasma is increased 5- to 10-fold in normal pregnancy)
Explain how T enters the cell, being converted to DHT (what enzyme? Where does it reside?), and the conversion of T to E (estrogen) in the brain (what enzyme?).
- T enters the cell via passive diffusion and binds to androgen receptor in the nucleus (AR)
- At the urogenital sinus, T is converted to DHT by an enzyme called 5-alpha-reductase which is located on the nuclear membrane
- In the brain, T can be converted to E by aromatase (this will be important in the masculinization of the brain (E masculinizes the brain not T!)
T is the dominant androgen in what tissues?
- Wolffian Duct
- Pituitary
- Kidney
What is DHT? What receptor does it bind to? What three ways does it amplify T action?
- A downstream metabolite of T that is 100x more potent than T
- Both DHT and T bind to the same AR (androgen receptor)
- 1) Conversion of testosterone to DHT is irreversible and … unlike testosterone, it cannot be converted to estrogens.
- 2) DHT has a higher affinity for the androgen receptor than does testosterone.
- 3) The DHT receptor complex is transformed more efficiently to the DNA binding state than is the testosterone receptor complex.
Embryologically the Testes differentiate from what cells? When? (This is a bird’s eye view, included because it is in the notes.)
- The testis differentiates in the embryo from a ridge of mesodermal cells next to the primitive kidney.
- Tubular structures, precursors of the seminiferous tubules, develop at about 8 weeks of age in the human fetus.
Where is the SRY gene located? What is it?
• The SRY gene (sex-determining region Y chromosome gene) has been identified on the short arm of the Y chromosome and is believed to be responsible for testicular differentiation.
What are the to main endocrine functions of the fetal testis? (This will be broken down)
- 1) Production of a Mullerian inhibiting factor (MIF) (also called antimullerian hormone, AMH) by the Sertoli cells that prevents the development of the Mullerian system and permits the subsequent differentiation of the mesonephros and Wolffian ducts. In the absence of this factor, the Mullerian ducts develop into the Fallopian tubes and uterus.
- 2) The second function during fetal development is the production of testosterone which is responsible for virilization of the Wolffian ducts into the epididymis, vas deferens and seminal vesicles. The testosterone metabolite, dihydrotestosterone (DHT), is formed within the urogenital sinus and lower genital tract from circulating testosterone. It acts in the urogenital sinus to induce formation of the male urethra and prostate and in the genital tubercle to cause the midline fusion, elongation, and enlargement that becomes the male external genitalia.
In the presence of the SRY gene, sertoli cells produce and secrete __(hormone)_ which has what affect on the embryological gonads?
In the absence of SRY, what happens to the embryological gonads?
- Sertoli cells produce Mullerian inhibiting factor (MIF) aka antimullerian hormone, AMH ==> inhibits Mullerian ducts and permits the subsequent differentiation of the mesonephros and Wolffian ducts.
- In the absence of SRY ==> MIF aka AMH, the Mullerian ducts develop into the Fallopian tubes and uterus and the Wolfian ducts degrade. Wolfian ducts need an adequate amount of T to be sustained.
Embryologically, where is T converted to DHT? What is the effect of DHT? What does T do? (actually not sure about this last question: whether T or DHT does this action)
- The testosterone metabolite, dihydrotestosterone (DHT), is formed within the urogenital sinus and lower genital tract from circulating testosterone.
- DHT acts in the urogenital sinus to induce formation of the male urethra and prostate and in the genital tubercle to cause the midline fusion, elongation, and enlargement that becomes the male external genitalia
- T converts Wolffian ducts into the epididymis, vas deferens and seminal vesicles.
When does sexual dimorphism become apparent in fetal development?
• Sexual dimorphism of the human gonad first becomes apparent with the appearance of seminiferous cords in the fetal testis between 6 and 7 weeks of gestation.
Explain the “pituitary take over” in terms of regulating T production in fetal development? (i.e how is T regulated before the pituitary is developed?)
- Since the testis is differentiated by 8 weeks, it precedes hormonal secretion of the anterior pituitary by 3-4 weeks.
- Thus it appears that the testis is initially independent of pituitary control.
- However, since the secretion of human chorionic gonadotropin (hCG) reaches a maximum level at 8-10 weeks of pregnancy, testosterone production may be stimulated by the small fraction of hCG which crosses the placenta.
- Pituitary “takeover” of the testis occurs some time after 8-12 weeks of gestation and is essential for normal testicular growth and testosterone production in later fetal life.
What is testicular feminization?
• General female phenotype with XY genotype
What are the two main causes of testicular feminization?
- Androgen Receptor (AR) deficiency
* 5-alpha-reductase deficiency (no conversion of T to DHT)
What are the subtypes of Androgen Receptor (AR) deficiency?
- Low AR levels
- Low high-affinity AR levels
- Normal AR levels but problems with nuclear translocation of androgen-AR complex
What are the clinical features of testicular feminization? (Structures here. Hormone levels next) Where are the testes? What do the external genitalia look like? What happens to the body during puberty?
- Testes are often located in the labia majora, inguinal canals, or intra-abdominally.
- The external genitalia are female, although the vagina is shallow and ends as a blind pouch.
- In adolescence, female secondary sex characteristics develop, notably with well-developed breasts and rounding of body contours.
What are the clinical features of testicular feminization? (Hormone levels)
- In AR deficiency, levels of testosterone in plasma, urine and spermatic venous plasma are within the range for normal males while estrogen levels in plasma and urine are in the lower range of normal for females.
- This syndrome is the result of a biochemical lesion that prevents the action of testosterone at that cellular level.
