Male Physiology Flashcards
Spermatogenesis
- Male germ cell compartment constitutes a stem cell population
- Mitosis begins in embryo
- Mitosis and meiosis occur throughout adult life
- Spermatogenesis occur in seminiferous tubules of testes
Spermatogenesis staggered throughout seminiferous tubules
Spermatogenic wave is defined as time it takes for reappearance of same stage within given segment
- each stage of wave follows in orderly sequence
- production of sperm in waves ensures spermatozoa are produced continuously
Spermatogenesis
(+) correlated with testosterone levels
- continous through life -> decreases with age
- can be affected by temp for up to 2 months post insult
Hypothalamo-Pituitary gonadal axis
GnRH –> FSH and LH
- FSH -> (on sertoli cells) cell products, androgen-binding protein, and inhibin (- feedback to FSH)
- LH –> (on leydig cells) testosterone
- testosterone inhibits negatively on LH and GnRH, but positively on sertoli
Relationship between leydig cells and sperm
Positive linear relationship between # of leydig cells and sperm production
Andropause
- Decreased testicular function -> loss of spermatocytes, leydig cells, sertoli cells, decreased testosterone production
- Symptoms -> +/- erectile function, weight gain
- Diagnosis -> measuring morning total testosterone
- Treatment -> hormone replacement, sleep, eat, exercise
Natural Androgens
Testosterone is potent testicular androgen -> 95% made by leydig cells
- testosterone converted to DHT (5alpha-reductase)
- SHBG binds androgens and estrogens
Androgen Functions
Promote health and function of:
- seminal vesicle, prostate, genital tract, external genitalia, hair growth, voice
Anabolic effects:
- muscle building, bone growth and closure of epiphysis, sodium and water retention
Synthetic Androgens
Oral, pellets, patch, transbuccal
- 1st pass metabolism for natural androgens, reduce first pass for synthetics
Methyl testosterone
C-17alpha-alkyl substitution -> orally active, esterification retards absoprtion, retards metabolism, hepatotoxic
Oxandrolone
C-17alpha-alkyl substitution (DHT derivative)
- cannot be converted by aromatase, lowers hepatotoxicity
- anabolic steroid -> muscle growth
Adverse effects of Androgens
Growth interruption (bone closure)
- priapism = massive erection
- sodium/water retention
- jaundice
- hepatic carcinoma
- hypogonadism
- aggressive behavior
- urinary obstruction
Why all the side effects?
they bind multiple receptors –> multiple effects
Medical Castration
Purpose - interfere with precocious puberty, treat androgen dependent cancers, reduce libido
- androgen receptor antagonists
- nonpulsatile GnRH agonists
- nonpulsatile GnRH antagonists
Intracrinology
Women -> all estrogens and androgens made locally in tissue from DHEA
Men -> testosterone made in testis, other androgens produced by adrenals
*GnRH agonists/antagonists wipe out testicular production, doesn’t effect other tissues
Androgen Antagonists
Flutamide, Bicalutamide, Nilutamide
- nonsteroidal pure receptor antagonist
- advanced prostate cancer
S.E. = gynecomastia, hepatotoxicity
GnRH agonists
Bind GnRH receptors and stimulate release of FSH, LH for therapeutic purposes (continous administration shuts down the HPG axis)
Gonadorelin -> assessment of gonadal response
Leuprolide -> synthetic analog of GnRH
- castration for cancer (continuous administration)
GnRH antagonists
Bind to GnRH receptors in anterior pituitary -> block action of GnRH -> reduces FSH, LH -> reduces testosterone production
Degarelix -> advanced prostate cancer, BPH
Ganirelix, Cetrorelix
No immediate androgen flare like the GnRH agonists
5-alpha reductase inhibitors
inhibits conversion of testosterone to DHT (specific androgen for growth and maintenance of prostate)
- BPH, prostate cancer, male patterned baldness
Finasteride -> 50% metabolized, 50% excreted in feces
Dutaseride
Physiology of Erection
- PS stimulation -> relaxation via NO
- NO binds receptors on VSM
- increases intracellular cGMP
- cGMP promotes arteriole dilation
- PDE-5 in VSM degrades cGMP
- Vasodilation ensues -> flaccid penis
PDE-5 inhibitors
Sildenafil
- prevents degradation of cGMP
- orally effective, headache, flushing, dyspepsia, nasal congestion
- don’t use with nitrates or alpha-blockers
