Cited by 402Sexual Differentiation and DisordersAdrenal Hormones and DisordersHormonal and reproductive studies

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

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Jenkins, E P, Andersson, S, Imperato-McGinley, J, Wilson, J D, Russell, D W·1992·Journal of Clinical Investigation

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.

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Crossref · 10.1172/jci115574

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Research works printed but not linked: 3

  1. Griffin, J. E., and J. D. Wilson. 1989. The androgen resistance syndromes: 5a-reductase deficiency, testicular feminization, and related disorders. In The Metabolic Basis of Inherited Disease. C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, editors. McGraw-Hill Inc., New York. 1919-1944.
  2. Andersson, S., and D. W. Russell. 1990. Structural and biochemical prop- erties of cloned and expressed human and rat steroid Sa-reductases. Proc. Nadt. Acad. Sci. USA. 87:3640-3644.
  3. Segel, I. H. 1975. Behavior and analysis of rapid equilibrium and steady- state enzyme systems. In Enzyme Kinetics. Wiley & Sons, New York. 1-957.

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Authors
Jenkins, E. P., Andersson, S., Imperato-McGinley, J., Wilson, J. D., & Russell, D. W.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Cornell University (US)
Venue
Journal of Clinical Investigation
Published
1992-01-01
Volume
89
Issue
1
Pages
293-300
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1974392957
Cited by
395
References
32
Citations by year
2026: 2 · 2024: 6 · 2023: 15 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 11 · 2012: 8
FWCI
11.26
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Welch Foundation (I-0971)
  • National Institutes of Health (5r01gm043753-07, 5r01dk003892-40)
  • National Institute of General Medical Sciences (GM-43753)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-03892, DK-07307, T32DK007307)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
5α-reductase, isozymes, dihydrotestosterone, 5-alpha-reductase deficiency, 46,XY disorders of sex development, finasteride, enzyme inhibition, pH optimum, cDNA, androgen production
MeSH terms
Base Sequence, Cloning, Molecular, DNA, Single-Stranded, Humans, Isoenzymes, Kinetics, Male, Molecular Sequence Data, Pedigree, Prostate, Polymorphism, Restriction Fragment Length, Disorders of Sex Development, Skin, Dihydrotestosterone, Testosterone, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Polymerase Chain Reaction

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