Pharmacology of Gonadal Hormones 2

Question 1

List and describe the structures of gonadotropins and their recombinant forms.

Answer 1

• FSH, LH, hCG
• Glycoproteins with alpha and beta subunits
  
  • beta subuint confers specificity
• Recombinant FSHs (follitropin alpha and follitropin beta) differ in their carbohydrate components.
• LH and hCG are available as recombinant proteins (lutropin alpha, chorionogonadotropin alpha) or as the biological material (urine derived)

Question 2

What is the mechanism of gonadotropins?

Answer 2

• Acts through G protein-coupled membrane receptors in testis
• cAMP is the principle 2nd messenger

Question 3

What cells do FSH primarily act on in the male? What is the effect? What about LH?

Answer 3

• FSH acts on Sertoli cells
  
  • promotes spermatogenesis
  • peromotes secretion of Androgen Binding Protein
• LH acts on Leydig cells
  
  • stimulates side-chain cleavage of cholesterol
    
    • rate limiting step in testosterone synthesis
  • crossover between effects of FSH and LH

Question 4

What are the diagnostic uses of gonadotropins in males?

Answer 4

• Determine whether delayed puberty is due to primary gonadal failure
• Evaluate Leydig cell function
  
  • hCG injected and testosterone measured
  • normal response indicates a problem at the hypothalamus or pituitary rather than primary gonadal failure

Question 5

What are the therapeutic uses are gonadotropins in males?

Answer 5

• Induce spermatogenesis in men with hypogonadotropic hypogonadism from hypothalamic or pituitary disease
  
  • FSH and LH given by injection
  • Response is slow, 4-6 months

Question 6

What are the uses of FSH, LH, and hCG in the female?

Answer 6

• Sequentially to induce ovulation and infertility treatment
  
  • FSH - induce follicular development
  • hCG/LH - induce oocyte maturation
  • success rate ~75%
• Used together with GnRH agonists to generate oocytes for in vitro fertilization

Question 7

What are the adverse effects of gonadotropin use.

Answer 7

• Gynecomastia in men
• Ovarian enlargement and multiple births in women