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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Preferential metabolism of dihydrotestosterone to androstanediol 17-glucuronide in rat prostate.

Androstanediol glucuronide (Adiol G), a marker of peripheral dihydrotestosterone (DHT) metabolism and action, may be conjugated through the hydroxyl group at either the 3-carbon (Adiol 3-G) or 17-carbon (Adiol 17-G) position. Adiol 17-G is the predominant Adiol G isomer derived from DHT in normal men. To determine whether peripheral tissues may be responsible for this selective conversion of DHT to Adiol 17-G, a glucuronyl transferase assay was developed using rat prostate cells. Adiol 17-G was separated from Adiol 3-G by HPLC and selective precipitation with an antibody specific for Adiol 3-G. Using androstanediol (Adiol) as a substrate, enzyme kinetics were linear with respect to time and enzyme concentration. In the presence of 0 or 5 microM Adiol and 1 microCi [3H]Adiol, greater than 99% of the resulting Adiol G was Adiol 17-G. The percent conversions of DHT, Adiol, and androsterone to their glucuronide conjugates were 0.22%, 3.5%, and 0.24%/10(6) prostate cells, respectively. Using DHT as an inhibitor of Adiol glucuronidation, the Ki was 39.1 microM, compared to an apparent Km for Adiol of 15 microM. We conclude that rat prostate cells can selectively convert Adiol to Adiol 17-G, and that Adiol glucuronidation is favored over that of DHT or androsterone under these experimental conditions. Since DHT and Adiol are readily interconvertable, these results suggest that Adiol 17-G is the major DHT metabolite in the rat prostate.[1]

References

  1. Preferential metabolism of dihydrotestosterone to androstanediol 17-glucuronide in rat prostate. Rittmaster, R.S., Leopold, C.A., Thompson, D.L. Endocrinology (1988) [Pubmed]
 
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