Endocrine and Biochemical Studies in a 46,XY Phenotypically Male Infant with 17-Ketosteroid Reductase Deficiency*

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Abstract
A 46,XY phenotypically male patient with 17-ketosteroid reductase deficiency is described. The patient was a 6-mo.-old infant who presented with micropenis and bilateral cryptorchidism. Baseline plasma levels of testosterone (T), .DELTA.4-androstenedione (.DELTA.4A), and 5.alpha.-dihydrotestosterone (5.alpha.-DHT) were within the normal range [patient:0.17 (T), 0.12 (.DELTA.4A), and 0.032 (5.alpha.-DHT) ng/ml; normal infants: 0.03-0.55 (T), 0.14-0.45 (.DELTA.4A), and 0.01-0.23 (5.alpha.-DHT) ng/ml]. hCG [chorionic gonadotropin] administration induced a significant rise in plasma .DELTA.4A levels (up to 8.39 ng/ml) and a slight increase in T and 5.alpha.-DHT levels. The .DELTA.4A/T ratios before and during the hCG challenge were 0.86 and 55.61, respectively (controls: 0.83 and 0.13). Incubation of genital skin-derived fibroblasts from the patient with either [3H]T or [3H].DELTA.4A revealed normal formation of .DELTA.4A from T and diminished conversion of .DELTA.4A to T. The development of a male phenotype despite both a testicular and peripheral 17-ketosteroid reductase deficiency is difficult to explain. It is possible that the fetal testes were the source of sufficient amounts of T during the early periods of embryonic life, and that late onset of the enzyme deficiency prevented the development of completely normal male genitalia. The in vitro finding of normal T to .DELTA.4A conversion by the mutant fibroblasts suggests that in this particular tissue 17.beta.-reduction and dehydrogenation of androgens are mediated by 2 isoenzymes with distinct substrate and/or cofactor specificities.