Reproductive Endocrinology in the Male

Question 1

Role of Leydig (interstitial) cells

Answer 1

• Produce androgens when stimulated by LH
  
  • 95% of Testosterone
• T synergizes with FSH to stimulate formation of ABP in Sertoli cells
• Synthesis of StAR, SCP, SAP
  
  • Help cholesterol get into cell and make steroids
• Required for spermiogenesis
• Have LH receptors (G_s)

Question 2

Role of Sertoli (supporting) cells

Answer 2

• Form blood-testis barrier via tight junctions
• Produces androgen binding protein (ABP)
  
  • Dramatically increases effectiveness of testosterone
• Nurture gametes (47 spermatozoa/Sertoli cell)
• Have FSH receptors (G_s)
  
  • Produces estrogens from T via aromatase
  • Produces inhibin and other growth factors
• Support Leydig cells with growth factors + inhibin

Question 3

HPT axis

Answer 3

• GnRH stimulates production of FSH and LH from pituitary
• LH acts on Leydig cells
  
  • Increased testosterone
  • Increased StAR, SCP, and SAP
• FSH acts on Sertoli cells
  
  • Increased androgen binding protein (ABP)
  • Increased aromatase
  • Increased growth factors
  • Increased spermatogenesis
  • Increased inhibin

Question 4

Role of HPG axis

Answer 4

• Males: pulsatile GnRH release leads to pulsatile releases of FSH and LH
• Females: FSH and LH secretion based on menstrual cycle
• Androgens inhibit release of GnRH, LH
• Sertoli cells release:
  
  • Growth factors to Leydig cells –> increased Leydig cell proliferation –> increased androgen release –> increase Sertoli actions
  • Inhibin which suppresses FSH
• FSH and LH share an a-subunit with TSH and hCG
  
  • hCG does jobs of FSH and LH early in embryonic development (< 14 weeks)
  • B subunits of FSH and LH responsible for individual activities of these hormones
  • hCG also responsible for embryonic testosterone formation

Question 5

Forms to which testosterone is converted

Answer 5

• Testosterone itself
• Dihydrotestosterone
  
  • via 5a-reductase
• Estrogen
  
  • via aromatase

Question 6

Locations of receptors of testosterone forms

Answer 6

• Testosterone
  
  • Androgen receptor
    
    • Muscles, reproductive organs
• Dihydrotestosterone
  
  • Androgen receptor, with higher affinity
    
    • External genitalia, sebaceous glands, hair follicles
• Estrogen
  
  • Estrogen receptor
    
    • Bone, adipose tissue, brain

Question 7

Functions of testosterone

Answer 7

• Pubertal development of penis
• Pubertal development of seminal vesicles
• Sperm production
• Causes male voice to deepen
• Imprint male sex drive, behavior
• Intrauterine differentiation
• Contributes to
  
  • Increased abdominal visceral fat
  • Increased muscle mass
  • Increased RBCs
  • Long bone growth
• Acts at liver to
  
  • Increase VLDL
  • Increase LDL
  • Decrease HDL
• Inhibition of breast growth
• Negative feedback on gonadotropins, GnRH
• Stimulation of ABP synthesis in Sertoli cells

Question 8

Functions of DHT

Answer 8

• Sebaceous gland formation
• Male pattern hair growth
• Development of prostate
• Pubertal development of penis
• Pubertal development of seminal vesicles
• Sperm production
• Feedback on gonadotropins
• Imprint male sex drive, behavior

Question 9

Functions of estrogen in the male

Answer 9

• Negative feedback on gonadotropins, GnRH
• Bone growth
• Sperm production

Question 10

Changes that take place in male at puberty

Answer 10

• Increased GH and testosterone
• Growth spurt usually 11 inches
• Boys get taller than girls, higher muscle mass, higher skeletal and lean body mass, more muscle cells, less body fat

Question 11

Roles of GH and sex steroids in bone growth

Answer 11

• T and E2 stimulate GH secretion and growth
  
  • Increases IGF-1
  • In absence of androgens, GH causes balanced growth and ossification
• Testosterone accelerates bone growth, differentiation (maturation), promotes epiphyseal closure, narrows growth window
  
  • Accomplishes this through estrogen action - aromatase is in bone so T2 –> E2 responsible for these actions
  • High levels of androgens cause accelerated growth, but also accelerated closure and short stature overall