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In Vitro Steroid Metabolic Studies in Testicular 17β-Reduction Deficiency

U. GOEBELSMANN, T. D. HALL^*, W. L. PAUL and F. Z. STANCZYK

Department of Obstetrics and Gynecology, University of Southern California School of Medicine Los Angeles, California

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 (⁵P), 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 ⁵P along ⁵- and ⁴-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.

Presented, in part, at the Twenty-first Meeting of the Society For Gynecologic Investigation, March 26–28, 1974, Los Angeles, California.

^* Part of this study was submitted as a dissertation in partial fulfillment of the requirements for the Doctor of Philosophy. Present address: Department of Medicine, University of Southern California, School of Medicine, Los Angeles, California.

BioScience Laboratories, Van Nuys, California.

Received May 7, 1975.