Editing Male Reproductive Physiology (section)

==Testosterone==

*'''<span style="color:#ff0000">Most important circulating androgen'''

=== <span style="color:#ff0000">Production ===
*'''90% produced by the testes and 10% by the adrenals'''
*'''<span style="color:#ff0000">Normal testosterone production is 5 g/day'''

=== <span style="color:#ff0000">Circulation ===
* '''<span style="color:#ff0000">Circulates in bound (98%) and free (2%) form'''
*'''<span style="color:#ff0000">Binding proteins (3):'''
*# '''<span style="color:#ff0000">Albumin (50%, loosely-bound)'''
*#'''<span style="color:#ff0000">Sex hormone-binding globulin ([SHBG], 44%, tightly-bound)''' 
*#*Produced in the liver
*#'''<span style="color:#ff0000">Corticotropin-binding globulin (4%, loosely-bound)'''
*'''<span style="color:#ff0000">The free and loosely-bound (albumin, corticortropin-binding) testosterone fractions combined are known as bioavailable testosterone<span style="color:#ff0000">'''
**<span style="color:#ff0000">'''Only bioavailable testosterone can enter cells and have an effect on the androgen receptor.'''
**Free and total testosterone measurements are most accurate when done by equilibrium dialysis but in the absence of this assay, they can be calculated from total testosterone, SHBG and albumin.
** <span style="color:#ff0000">'''Serum testosterone levels <300 ng/dL considered low'''
**Calculated free testosterone <6.5 ng/dL considered low
**Intratesticular testosterone levels are 50-100x those of the circulating serum levels and are necessary for appropriate spermatogenic function.
*'''SHBG'''
**'''<span style="color:#ff0000">Conditions associated with decreased SHBG (so expect higher proportion of bioavailable testosterone for same total testosterone level)'''
**#'''<span style="color:#ff0000">Obesity'''
**#'''<span style="color:#ff0000">Nephrotic syndrome''' 
**# '''<span style="color:#ff0000">Hypothyroidism'''
**#'''<span style="color:#ff0000">Use of glucocorticoids, progestins, and androgenic steroids'''
**#'''<span style="color:#ff0000">Acromegaly''' 
**#'''<span style="color:#ff0000">Diabetes mellitus'''
**'''<span style="color:#ff0000">Conditions associated with increased SHBG [so expect lower proportion of bioavailable testosterone for same total testosterone level]'''
**#'''<span style="color:#ff0000">Aging''' 
**#'''<span style="color:#ff0000">Hepatitis and cirrhosis/liver failure'''
**#'''<span style="color:#ff0000">Hyperthyroidism'''
**#'''<span style="color:#ff0000">Use of anticonvulsants'''
**#'''<span style="color:#ff0000">Use of estrogens'''
**#'''<span style="color:#ff0000">HIV'''

=== <span style="color:#ff0000">Metabolism</span> ===
*'''Occurs primary in the liver'''
* '''<span style="color:#ff0000">Metabolized by</span>''' 
*#'''<span style="color:#ff0000">Aromatase into estradiol</span>'''
*#*<span style="color:#ff0000">'''Estradiol (E2)'''</span>''' 
*#**<span style="color:#ff0000">'''Inhibits LH secretion'''</span>
*#***<span style="color:#ff0000">'''Most potent regulator of the HPG axis in the male'''</span>
*#**<span style="color:#ff0000">'''Promotes bone health and libido'''</span>
*#'''<span style="color:#ff0000">5α-reductase to dihydrotestosterone (DHT), mainly in the target organs'''
*#*<span style="color:#ff0000">'''Following passive diffusion through the cell membrane into the cytoplasm, testosterone undergoes conversion to dihydrotestosterone (DHT) through the action of the enzyme 5α-reductase'''
*#*'''<span style="color:#ff0000">Both testosterone and DHT exert their biologic effects by binding to the AR in the cytoplasm,</span>''' promoting the association of AR coregulators. '''<span style="color:#ff0000">The complex then translocates to the nucleus and binds to androgen response elements in the promoter regions of target genes'''
*#*'''The relative potency of testosterone and DHT are similar''' '''(as defined by''' the ability to cause half-maximal response in a prostate regrowth model), '''however,''' '''if the conversion of testosterone to DHT is blocked by the 5α-reductase inhibitor finasteride, 13-fold more testosterone is required for the same effect'''.
*#*'''DHT is in high concentrations in the prostate and hair follicles'''
*#* '''<span style="color:#ff0000">Isoforms of 5α-reductase (2):'''
*#*#'''<span style="color:#ff0000">Type 1: localized in the non-genital skin, liver, brain, prostate, and testis'''
*#*#*'''<span style="color:#ff0000">Inhibited by finasteride and dusteride'''
*#*#'''<span style="color:#ff0000">Type 2: active in the classical androgen-dependent tissues (epididymis, genitalia, seminal vesicle, testis, and prostate) but also in liver, uterus, breast, hair follicles, and placenta'''
*#*#* '''<span style="color:#ff0000">Inhibited by dutasteride'''
*'''Half-life of testosterone in plasma is 12 minutes'''
*Testosterone and DHT contribute to muscle, bone, skin, sperm, brain, nerve development and hematopoiesis.