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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
lowTengineer looking for help
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<blockquote data-quote="madman" data-source="post: 141924" data-attributes="member: 13851"><p><span style="color: rgb(0, 0, 0)"><strong>The </strong></span><span style="color: rgb(184, 49, 47)"><strong>amplification pathway converts ~4% </strong></span><span style="color: rgb(0, 0, 0)"><strong>of circulating testosterone to the more potent, pure androgen, DHT (50, 52).</strong></span> DHT has higher binding affinity to (109) and 3-10 time greater molar potency in transactivation (110-112) of the androgen receptor relative to testosterone. <strong><span style="color: rgb(184, 49, 47)">Testosterone is converted to the most potent natural androgen DHT by the 5a-reductase enzyme that originates from two distinct genes (I and II) (113). </span>Type 1 5a-reductase is expressed in the liver, kidney, skin, and brain, whereas <span style="color: rgb(184, 49, 47)">type 2 5a-reductase is characteristically expressed strongly in the prostate but also at lower levels in the skin (hair follicles) and liver (113). </span></strong>Congenital 5a-reductase deficiency due to mutation of the type 2 enzyme protein (114) leads to a distinctive form of genital ambiguity causing under masculinization of genetic males, who may be raised as females, but in whom puberty leads to marked virilization including phallic growth, normal testis development and spermatogenesis (115) and bone density (116) as well as, occasionally, masculine gender reorientation (117). Prostate development remains rudimentary (118) and sparse body hair without balding is characteristic (119). This remarkable natural history reflects the dependence of urogenital sinus derivative tissues on strong expression of 5a-reductase as a local androgen amplification mechanism for their full development. This amplification mechanism for androgen action was exploited in developing azasteroid 5a-reductase inhibitors (120). As the type 2 5a-reductase enzyme results in over 95% of testosterone entering the prostate being converted to the more potent androgen DHT (121), blockade of that isoenzyme (the expression of which is largely restricted to the prostate) confines the inhibition of testosterone action to the prostate (and other urogenital sinus tissue derivatives) without blocking extra-prostatic androgen action. <strong>DHT <span style="color: rgb(184, 49, 47)">circulates at ~10% of blood testosterone concentrations,</span> due to spillover from the prostate (122-123) and nonprostatic sources (124). </strong>Whereas genetic mutations disrupting type 2 5a-reductase produce disorders of urogenital sinus derived tissues in men and mice (125), genetic inactivation of type 1 5a-reductase has no male phenotype in mice and no mutations of the human type 1 enzyme have been reported. Whether this reflects the type I enzyme having an unexpected phenotype or an evolutionarily conserved vital function, remains unclear. A third 5a-reductase enzyme (type 3, SRD5A3) has been described (126) but is widely expressed in human tissues, lacks steroidal 5a-reductase activity and has other roles in fatty acid metabolism (127).</p><p>------------------------------------------------------------------------------------------------------</p><p></p><p></p><p></p><p></p><p></p><p>Take home point:</p><p></p><p><span style="color: rgb(0, 0, 0)"><strong>The </strong></span><span style="color: rgb(184, 49, 47)"><strong>amplification pathway converts ~4% </strong></span><span style="color: rgb(0, 0, 0)"><strong>of circulating testosterone to the more potent, pure androgen, DHT (50, 52).</strong></span></p><p></p><p><strong>DHT <span style="color: rgb(184, 49, 47)">circulates at ~10% of blood testosterone concentrations,</span> due to spillover from the prostate (122-123) and nonprostatic sources (124). </strong></p></blockquote><p></p>
[QUOTE="madman, post: 141924, member: 13851"] [COLOR=rgb(0, 0, 0)][B]The [/B][/COLOR][COLOR=rgb(184, 49, 47)][B]amplification pathway converts ~4% [/B][/COLOR][COLOR=rgb(0, 0, 0)][B]of circulating testosterone to the more potent, pure androgen, DHT (50, 52).[/B][/COLOR] DHT has higher binding affinity to (109) and 3-10 time greater molar potency in transactivation (110-112) of the androgen receptor relative to testosterone. [B][COLOR=rgb(184, 49, 47)]Testosterone is converted to the most potent natural androgen DHT by the 5a-reductase enzyme that originates from two distinct genes (I and II) (113). [/COLOR]Type 1 5a-reductase is expressed in the liver, kidney, skin, and brain, whereas [COLOR=rgb(184, 49, 47)]type 2 5a-reductase is characteristically expressed strongly in the prostate but also at lower levels in the skin (hair follicles) and liver (113). [/COLOR][/B]Congenital 5a-reductase deficiency due to mutation of the type 2 enzyme protein (114) leads to a distinctive form of genital ambiguity causing under masculinization of genetic males, who may be raised as females, but in whom puberty leads to marked virilization including phallic growth, normal testis development and spermatogenesis (115) and bone density (116) as well as, occasionally, masculine gender reorientation (117). Prostate development remains rudimentary (118) and sparse body hair without balding is characteristic (119). This remarkable natural history reflects the dependence of urogenital sinus derivative tissues on strong expression of 5a-reductase as a local androgen amplification mechanism for their full development. This amplification mechanism for androgen action was exploited in developing azasteroid 5a-reductase inhibitors (120). As the type 2 5a-reductase enzyme results in over 95% of testosterone entering the prostate being converted to the more potent androgen DHT (121), blockade of that isoenzyme (the expression of which is largely restricted to the prostate) confines the inhibition of testosterone action to the prostate (and other urogenital sinus tissue derivatives) without blocking extra-prostatic androgen action. [B]DHT [COLOR=rgb(184, 49, 47)]circulates at ~10% of blood testosterone concentrations,[/COLOR] due to spillover from the prostate (122-123) and nonprostatic sources (124). [/B]Whereas genetic mutations disrupting type 2 5a-reductase produce disorders of urogenital sinus derived tissues in men and mice (125), genetic inactivation of type 1 5a-reductase has no male phenotype in mice and no mutations of the human type 1 enzyme have been reported. Whether this reflects the type I enzyme having an unexpected phenotype or an evolutionarily conserved vital function, remains unclear. A third 5a-reductase enzyme (type 3, SRD5A3) has been described (126) but is widely expressed in human tissues, lacks steroidal 5a-reductase activity and has other roles in fatty acid metabolism (127). ------------------------------------------------------------------------------------------------------ Take home point: [COLOR=rgb(0, 0, 0)][B]The [/B][/COLOR][COLOR=rgb(184, 49, 47)][B]amplification pathway converts ~4% [/B][/COLOR][COLOR=rgb(0, 0, 0)][B]of circulating testosterone to the more potent, pure androgen, DHT (50, 52).[/B][/COLOR] [B]DHT [COLOR=rgb(184, 49, 47)]circulates at ~10% of blood testosterone concentrations,[/COLOR] due to spillover from the prostate (122-123) and nonprostatic sources (124). [/B] [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Blood Test Discussion
lowTengineer looking for help
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