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Research Article

Metabolism of the B-Ring of Testosterone by the Rat Cytochrome P-450 System

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Pages 535-539 | Published online: 22 Sep 2008
 

Abstract

It was surprising to us to discover that testosterone could be converted to 17/3-hydroxy-4,6-androstadiene-3-one (Δ6-T) by liver microsomes from adult male rats [1], because at that time aromatase, which converts 4-androstene-3,17-dione to estrone [2], was the only isozyme of cytochrome P-450 known to catalyze the desaturation of an aliphatic substance. Subsequently, however, it was also discovered that the isozymes of cytochrome P-450 could also catalyze the desaturation of valproic acid to valproic-4-ene [3]. The ability of liver microsomes from rats to form Δ6-T was greatly increased by pretreating the rats with phenobarbital, pregnenolone-16a-carbonitrile, or dexamethasone. Indeed, the increases in Δ6-T formation were directly proportional to the increases in the formation of 6β-hydroxytestosterone, thereby suggesting that those isozymes that catalyze 6β-hydroxylation of testosterone were also able to catalyze the formation of A6-T but at much slower rates (approximately 10%).

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