In VitroSteroid Metabolic Studies in Testicular 17β-Reduction Deficiency

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Abstract
In order to document testicular 17β-reduction deficiency (17RD) and to search for additional metabolic aberrations possibly associated with this disorder, the metabolism of 14C-labeled pregnenolone (Δ5P), 17-hydroxyprogesterone (170HP), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and estrone (E1) was studied in testicular minces from a 46-year-old male pseudohermaphrodite (MPH) with highly elevated testicular A and minimal T secretion but normal extragonadal conversion of A to T. Testicular minces from a 20-year-old MPH with apparently normal testicular T biosynthesis served as a control. The results of this investigation show that the 17RD testes metabolized Δ5P along Δ5- and Δ4-pathways but, in contrast to the control, converted more 17OHP, metabolizing it predominantly to A rather than T, failed to reduce DHEA to androst-5-ene-3β,17β-diol, metabolized DHEA very efficiently to A and produced little T, and converted only minimal quantities of A and E1 to their 17β-reduced counterparts. 17β-Reduction increased slightly but was far from being restored to control levels upon addition of NADH plus NADPH. However, oxidation of T to A by 17RD testicular minces, with and without additional NAD plus NADP, was comparable to that by the control. These results document 17RD for A, DHEA and E1 and suggest that the lack of elevated 17OHP and DHEA secretion by the 17RD testes was due to increased 17, 20-lyase and perhaps elevated 3β-hydroxysteroid dehydrogenase and/or isomerase activity. The observation that 17β-reduction was only slightly increased upon addition of NADH plus NADPH, but that oxidation of T to A was normal, is consistent with the assumption that more than one 17β-hydroxysteroid dehydrogenase may be involved in testicular 17β-reduction and/or 17-oxidation, and that the 17RD testes studied either lacked the enzyme which acts predominantly as 17β-reductase or that the affinity of this 17β-reductase for reduced cofactor(s) and/or substrates was abnormal.

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