Pharmacology of Gonadal Hormones 2 Flashcards
Describe why and how gonadotropins are used therapeutically in males and females.
1
Q
List and describe the structures of gonadotropins and their recombinant forms.
A
- 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)
2
Q
What is the mechanism of gonadotropins?
A
- Acts through G protein-coupled membrane receptors in testis
- cAMP is the principle 2nd messenger
3
Q
What cells do FSH primarily act on in the male? What is the effect? What about LH?
A
- 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
- stimulates side-chain cleavage of cholesterol
4
Q
What are the diagnostic uses of gonadotropins in males?
A
- 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
5
Q
What are the therapeutic uses are gonadotropins in males?
A
- Induce spermatogenesis in men with hypogonadotropic hypogonadism from hypothalamic or pituitary disease
- FSH and LH given by injection
- Response is slow, 4-6 months
6
Q
What are the uses of FSH, LH, and hCG in the female?
A
-
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
7
Q
What are the adverse effects of gonadotropin use.
A
- Gynecomastia in men
- Ovarian enlargement and multiple births in women