GENETIC AND PHARMACOLOGICAL EVIDENCE FOR MORE THAN ONE HUMAN STEROID 5-ALPHA-REDUCTASE

The enzyme steroid 5-alpha-reductase catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone, and impairment of this reaction causes a form of male pseudohermaphroditism in which genetic males differentiate predominantly as phenotypic females. We previously isolated cDNA clones that encode a human steroid 5-alpha-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDNA is normal in subjects with the genetic disease steroid 5-alpha-reductase deficiency. We further show that in contrast to the major steroid 5-alpha-reductase in the prostate and cultured skin fibroblasts, the cDNA-encoded enzyme exhibits a neutral to basic pH optima and is much less sensitive to inhibition by the 4-aza steroid, finasteride (MK-906). The results provide genetic, biochemical, and pharmacological support for the existence of at least two steroid 5-alpha-reductase isozymes in man.