Deficient 17β-Hydroxysteroid Oxidoreductase Activity in Testes from a Male Pseudohermaphrodite

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Abstract
17β-Hydroxysteroid oxidoreductase (17β-HOR) activity in testicular tissue from a male pseudohermaphrodite (MP) who had elevated plasma LH and androstenedione (A) levels, and normal dehydroepiandrosterone (DHA) levels was compared by in vitro studies to that of testicular tissue from a normal man. The 17β-HOR activity from the MP was localized predominantly in the microsomal fraction, as it is in normal testicular tissue. With DHA, A, and estrone as substrates, the 17β-HOR activity of the MP was decreased in the presence of NADPH, but not NADH, in comparison with the normal. NADPH was the preferred co-factor for 17β-HOR from the normal testes, while 17β-HOR activity from the MP testes was less with NADPH than with NADH as cofactor. These results indicate that the inefficient testosterone production in the MP testes may be accounted for by a deficiency of NADPH-dependent 17β-HOR activity. Further studies suggested that 3β-hydroxysteroid oxidoreductase-isomerase (3β-HOR) was increased in the MP testes and was much greater than 17β-HOR activity with DHA as substrate. These findings largely explain the elevated plasma A levels with normal DHA levels, and suggest that DHA → A → testosterone was the major route of testosterone biosynthesis in the MP testes.

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