Male hormones, BPH, ED Flashcards
Dr. Pond
Name two types of cells in the testes contributing to spermatogenesis
Sertoli cells - receive FSH
Leydig cells (interstitial cells) - receive LH
What are the two hormones that stimulate spermatogenesis?
FSH: directly on Sertoli cells
Testosterone: produced by Leydig cells -> acting on Sertoli cells
Function of testosterone
-development and growth of reproductive organs and other tissues
-negative feedback on GnRH -> lowers FH and LH
-95% secreted by testis, 5% adrenal
Important Androgens
-Testosterone
-dihydrotestosterone (strong)
-androstenedione (weak)
-dehydroepiandrosterone (DHEA, weak)
In which tissues do we find DHT?
-Skin
-prostate
-seminal vesicles
-epididymis
Testosterone converted to DHT by 5-alpha reductase
-inhibiting 5-alpha reductase inhibits androgenic effects in these tissues
In which tissues does the conversion of testosterone to estradiol occur?
-Liver: higher level in the liver can lead to increased synthesis of clotting factors and angiotensin (blood pressure)
-adipose tissue
-hypothalamus: testosterone is converted to estrogen and cause negative feedback
Adverse effects of Testosterone
in males:
-acne, sleep apnea, erythrocytosis (high concentration of red blood cells), azoospermia, gynecomastia
general:
aggressiveness, jaundice, hepatic adenoma and carcinoma, prostatic hyperplasia
MOA Finasteride (Propecia)
for male pattern baldness, BPH, prostate cancer prevention, hirsutism in females
-blocks 5-alpha reductase -> preventing the conversion of testosterone to DHT
ADE Finasteride
-decreased libido/erectile dysfunction (since stimulated by androgens (here DHT))
-gynecomastia
-less common: rash, myopathy (long-term use)
Name 2 Androgen receptor antagonists
-Bicalutamide (partial agonist)
-Enzalutamide (full antagonist)
used for prostate cancer
MOA for Bicalutamide and Enzalutamide
Bicalutamide binds to AR but does not induce the correct conformational change -> CoR (repressor) binds and forms an inactive AR-DNA complex
-> in certain cases the tumor will mutate and the repressor acts as an activator
Enzalutamide binds to AR and shapes the AR in a way that the AR-DNA will not even form
Tissues regulating erection and ejaculation
Corpus sporangium: surrounds the urethra and forms the bulb of the penis -> maintains the opening of the urethra during ejaculation
Corpus cavernosa: paired dorsal erectil bodies
Which molecule is released in the tissues of the penis during sexual arousal?
parasympathetic nervous system reflex (usually releases acetylcholine -> binds to the muscarinic receptor)
but here:
-release of nitric oxide to cause vasodilation and expansion of the Corpus cavernosa and spongiosum
Causes of Erectile dysfunction
-heart diseases, clogged blood vessels (atherosclerosis), high BP -> since blood needs to flow to the penis
-diabetes, obesity
-neurological: Parkinson’s, multiple sclerosis
-hormonal disorder: low testosterone
-surgery in the pelvic area or spinal cord
Drugs causing ED
-blood pressure meds: diuretics, beta-blocker
-psychological disorder: anti-anxiety, anti-psychotics, anti-depressants (SSRIs)
-anti-androgens: gonadotropin-releasing hormone agonists (used in prostate cancer)
