64: Androgens

Question 1

GnRH is secreted in a pulsatile fashion every 30-120 min –>

Answer 1

LH release from Pit –>
testosterone release from leydig cells into the blood stream

negative feedback at ant. pit and hypothalamus

Question 2

leydig cells express ________ that converts androstenedione to testosterone

Answer 2

17B hydroxysteroid dehydrogenase

Question 3

converts testosterone to dihydrotestosterone

Answer 3

5a reductase

more potent androgen, higher binding affinity

Question 4

most testosterone in blood is bound to…

Answer 4

albumin or SHBG

the active form is free or bound to albumin

Question 5

anabolic effects of androgens

Answer 5

• stimulate basal metabolic rate
• inhibit lipid accumulation in adipocyts, stimulates lipolysis, inhibits differentiation of adipocyte precursors
• lowers blood glucose levels by increasing expression of glucose transproters
• reduces bone reabsorption and enhances bone formation
• increases production EPO
• increases prtn synthesis and inhibits prtn breakdown

Question 6

at puberty, ___ facilitates closure of epiphysial growth plate

Answer 6

estradiol

Question 7

therapeutic uses androgens

Answer 7

• replacement therapy in hypogonadal men
• aging
• stimulate sexual development and increase height of teenagers with delayed puberty
• severe endometriosis
• debilitated states

Question 8

causes of primary hypogonadism

Answer 8

• cryptochidism
• klinefelter syndrome
• chemotherapy

testicular dysfunction leading to a decrease in testosterone production. loss of neg. feedback causes an increase in circulating gonadotropins.

hypergonadotropic hypogonadism

Question 9

low testosterone in the setting of low LH and FSh

Answer 9

secondary hypogonadism

decrease in circulating gonadotrophins from hypo/pit probs or morbid obesity

hypogonadotropic hypogonadism

Question 10

MOA flutamide, bicalutamide, enzalutamide

Answer 10

competitive antagonists of androgen receptors

used to treat prostate cancer

causes mild gynecomastia

Question 11

additional effects of enzalutamide

Answer 11

• inhibits nuclear translocation of AR
• blocks DNA binding
• blocks coactivator recruitment

Question 12

MOA goserelin and leuprolide

Answer 12

GnRH agonists

initially increase LH and testosterone production bu tover time desensitize and downregulate GnRH receptors

used to treat prostate cancer

Question 13

MOA degarelix

Answer 13

GnRH antagonist

fast onset
no LH surge
reduces LH/FSH production and release
decrease testosterone production

Question 14

MOA abiraterone

Answer 14

androgen biosynthetic inhibitor (blocks 17alpha)

Question 15

MOA finasteride and dutasteride

Answer 15

5 alpha reductase inhibitors

reduces DHT levels

used to treat BPH, and androgenic alopecia

Question 16

bald man has decreased PSA - what do you need to check before jumping to conclusions?

Answer 16

is he taking a 5a reductase inhibitor like finasteride or dutasteride

lead to flase negatives with prostate CA

Question 17

mechanism of penile erection

Answer 17

sexual stimulation –> production NO –> increased activity guanylyl cyclase –> increased cGMP –> relaxation of smooth muscle of corpus cavernosum –> increased blood flow –> erection

Question 18

PDE5 inhibitors

Answer 18

sildenafil
vardenafil
tadalafil