Male Physiology Review

Question 1

Describe male reproductive function from conception to senescence:

Answer 1

1. Fetal testes secrete:
   
   • mullerian inhibiting factor
   • androgens (primarily testosterone)
   • burst in fetal testicular activity
2. Burst in gonadotropins
3. Puberty starts
4. Decline in male reproductive function with age is not nearly as dramatic (if it occurs at all) as in women
   
   • men can maintain reproductive function well into their 9th decade of life
   • However, a decrease in testosterone has been documented in the aging man

Question 2

1. What is the function of mullerian inhibiting factor (MIF)?
2. What is the role of the androgens secreted in the fetal testes?
3. What stimulates the burst in fetal testicular activity?

Answer 2

1. **Mullerian inhibiting factor **
   
   • induces the regression of the mullerian ducts
2. Androgens (primarily testosterone)
   
   • induces fetal differentiation into the male phenotype
3. Burst in fetal testicular activity
   
   • stimulated by LH and FSH

Question 3

What changes in reproduction occur around 6 months of age in males?

Answer 3

• Burst in gonadotropins
  
  • stimulates testosterone production that may induce sexual dimorphic changes in the brain

Question 4

What occurs during puberty in males?

Answer 4

• Pulsatile activity in GnRH neurons increases ⇒ LH and FSH bursts
• Increase in gonadotropins stimulates sperm production and steroidogenesis
• Pubertal increase in testicular androgen secretion induces the development of the male secondary sex characteristics

Question 5

Enzymes involved at each step:

Answer 5

1. CYP11A1 (side chain cleavage; P450scc)
2. 3‐ hydroxysteroid dehydrogenase (3HSD)
3. CYP17 (17‐hydroxylase; P450c17)
4. CYP17 (17,20‐lyase; P450c17)
5. 17‐HSD3 (17‐hydroxysteroid dehydrogenase 3; 17‐ketoreductase)
6. 5‐alpha‐reductase
7. CYP19 (aromatase)

Question 6

What happens to testosterone in peripheral tissues?

Answer 6

Converted to DHT

Question 7

Mechanism of Action for Testosterone (T):

Answer 7

• Plasma T must dissociate from its carrier proteins (sex hormone binding globulin and albumin) and diffuse into the cytoplasm
• There, it can be converted to DHT by 5‐alpha‐reductase
• T can bind to the androgen receptor (AR) in the nucleus
  
  • DHT has a higher affinity for the AR
• Like all steroid hormones, the transcription of androgen‐sensitive genes is increased by testosterone leading to the translation of mRNA and new protein

Question 8

Describe the general physiology of male puberty (5 steps):

Answer 8

1. Pulsatile GnRH release from the hypothalamus (like in the female)
   
   • Note: men do produce prolactin and, like women, it inhibits gonadotropin secretion
2. Testosterone induces an increase in GH release
   
   • stimulates linear growth (through IGF1)
   • salutary effects on spermatogenesis
3. Major stimulator of spermatogenesis:
   
   • combination of FSH stimulation and local testosterone stimulation
4. Testosterone induces the male secondary sex characteristics
5. Finally, testosterone (like estrogen in women) causes epiphyseal (growth plate) closure ending pubertal growth

Question 9

• LH primarily stimulates the ______ cell
• FSH primarily stimulates the ______ cell
• Leydig cell produces ___________ which:
  
  • What are the effects?
• Testosterone exrerts ________ feedback effects
• Inhibin produced by the Sertoli cell primarily inhibits only ___ release

Answer 9

• LH primarily stimulates the Leydig cell
• FSH primarily stimulates the Sertoli cell
• Leydig cell produces testosterone which
  
  • released into the blood and has systemic androgenic effects
  • local (intra‐testicular) effects to stimulate the sertoli cell
• Tesosterone exerts negative feedback effects (similar to estrogen)
• Inhibin produced by the sertoli cell primarily inhibits only FSH release

Question 10

Describe the control of steroidogenesis:

• What stimulates the Leydig cell?
• How is FSH response increased?
• What is the end result of these effectors?

Answer 10

• LH stimulates leydig cell steroidogenesis
• In addition to being released into the blood, testosterone diffuses into the sertoli cell where it increases the response to FSH
• Result is a stimulation of spermatogenesis

Question 11

• What increases ABP production?
• How does ABP affect the testosterone concentration?

Answer 11

• FSH and testosterone increase the production of androgen binding protein (ABP)
  
  • Completely distinct from SHBG in the blood (plasma protein binding of testosterone).
• ABP acts as a local “sink” for testosterone
  
  • greatly increases the local testosterone concentration
  • developing sperm are being bathed in very high concentrations of testosterone

Question 12

Describe the negative feedback loop for FSH:

Answer 12

FSH → ⊕inhibin → ∅FSH

Question 13

What is the major difference in function between testosterone and DHT?

Answer 13

• Testosterone
  
  • spermatogenesis
• DHT
  
  • prostatic secretion

Question 14

Fill in the blanks

Answer 14

Question 15

Describe the changes in male plasma testosterone throughout life:

Answer 15

1. Gestational spike
2. Fetal spike
3. Pubertal spike
4. Levels are maintained until old age
   
   • Even, a male can still be ferile into his 80’s
   • Infertility usually doesn’t begin to occur until sperm production is below 50%