Cited by 400Sexual Differentiation and DisordersAdrenal Hormones and DisordersHormonal and reproductive studies

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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

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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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BindingDB (2009) · UC San Diego · doi:10.7270/q2p84bkv
BindingDB Entry 50014938: Synthesis, biological activity, and three-dimensional quantitative structure-activity relationship model for a series of benzo[c]quinolizin-3-ones, nonsteroidal inhibitors of human steroid 5alpha-reductase 1.
BindingDB (2009) · UC San Diego · doi:10.7270/q24j0dkz
BindingDB Entry 50033377: Synthesis and bioactivity of new Finasteride conjugate.
BindingDB (2011) · UC San Diego · doi:10.7270/q2b56k2n
BindingDB Entry 50048451: Synthesis of benzanilide derivatives as dual acting agents with alpha 1-adrenoceptor antagonistic action and steroid 5-alpha reductase inhibitory activity.
BindingDB (2018) · UC San Diego · doi:10.7270/q2k35wvs
BindingDB Entry 50048440: A practical synthesis of 3-substituted delta 3,5(6)-steroids as new potential 5 alpha-reductase inhibitor.
BindingDB (2018) · UC San Diego · doi:10.7270/q20867gt
Untitled work
(1999) · doi:10.1002/(sici)1097-0045(19991201)41:4

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)
ORCID: Russell, D W
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1992-01-01
Volume: 89
Issue: 1
Pages: 293-300
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci115574
PMC: PMC442847
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: bronze
doi.org
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: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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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Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase.

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