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=== <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">5Ξ±-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 5Ξ±-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 5Ξ±-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 5Ξ±-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.
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