Abstract
Kinetic analyses of progesterone and androsienedione metabolism were performed in testicular tissue of 5 male pseudohermaphrodites (MPH) with familial 17-ketoreductase deficiency previously described (J. Steroid Blochem.. 19:663-674. 1983). and compared to 2 normal controls. The age of the patients ranged between 3-3/4 and 35 years. Testicular tissue was obtained during surgery tor male genitoplasty in 4 cases, and during castration in one individual, who had been reared unequivocally as a female. While the testicular tissue of the 2 prepubertal MPH metabolized progesterone to androstenedione only, and that in a limited extent, the 3 postpuberlal MPH metabolized progesterone to 16α- and 16β-hydroxyprogesterone (16-OHP). 17-hydroxyprogesterone. androsienedione and to testosterone. These MPH metabolized androsienedione to testosterone as well, to a comparable extent at the controls. The Michaelis constant of these reactions was similar for the MPH and the controls. An 7.8 to 12.8-fold increase in the production of 16-OHP, and a 4.6 to 11.5-fold inhibition of the 17-hydroxylase was found in the testes of the MPH. The preference of androsienedione production by the testes of 2 MPH was examined using a equimolar concentration of [14C]-progesterone and [H3]-pregnenolone as substrates. While the flow of substrates in the normal testes was equal or slightly preferable through the Δ-4 pathway, a more than 8-times preference of the Δ-5 pathway was noted in the testes of the MPH. A large accumulation of DHEA was found upon omission of NAD, the 3β-styeroid dehydrogenase-isomerase cofactor, supporting the contention that in MPH androsienedione is mainly produced through the Δ-5 pathway. Further support for this was the finding that the 3H/14C ratio of androsienedione and testosterone produced from both substrates was 8-times higher in MPH than in controls. MPH due to 17-ketoreductase deficiency appears to be a mixture of complex metabolic aberrations In the androgen biosynthetic pathway.
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Rösle, A., Eckstein, B., Cohen, S. et al. 143 IN VITRO METABOLIC STUDIES OF TESTICULAR TISSUE IN FAMILIAL MALE PSEUDOHERMAPHRODITISM DUE TO 17-KETOREDUCTASE DEFICIENCY. Pediatr Res 24, 541 (1988). https://doi.org/10.1203/00006450-198810000-00164
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DOI: https://doi.org/10.1203/00006450-198810000-00164
