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

Abstract

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.

• Authors: E P Jenkins, S Andersson, J Imperato-McGinley, J D Wilson, D W Russell
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 89 Issue 1 Pg. 293-300 (Jan 1992) ISSN: 0021-9738 [Print] United States
• PMID: 1345916 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Single-Stranded
• Isoenzymes
• Dihydrotestosterone
• Testosterone
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Topics

• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (deficiency, genetics)
• Base Sequence
• Cloning, Molecular
• DNA, Single-Stranded
• Dihydrotestosterone (metabolism)
• Disorders of Sex Development (ethnology, etiology, genetics)
• Humans
• Isoenzymes (genetics)
• Kinetics
• Male
• Molecular Sequence Data
• Pedigree
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Prostate (cytology, enzymology)
• Skin (cytology, enzymology)
• Testosterone (metabolism)