Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase.

E P Jenkins; S Andersson; J Imperato-McGinley; J D Wilson; D W Russell

doi:10.1172/JCI115574

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

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Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

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Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

Find articles by Imperato-McGinley, J. in: JCI | PubMed | Google Scholar

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

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Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.

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Published in Volume 89, Issue 1 on January 1, 1992
J Clin Invest. 1992;89(1):293–300. https://doi.org/10.1172/JCI115574.
© 1992 The American Society for Clinical Investigation

Published January 1, 1992 - Version history

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.

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