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Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism

Nature volume 354, pages 159161 (14 November 1991) | Download Citation

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Abstract

THE conversion of testosterone into dihydrotestosterone by steroid 5α-reductase is a key reaction in androgen action, and is essential both for the formation of the male phenotype during embryogenesis and for androgen-mediated growth of tissues such as the prostate1,2. Single gene defects that impair this conversion lead to pseudohermaphroditism in which 46 X, Y males have male internal urogenital tracts, but female external genitalia3. We have described the isolation of a human 5α-reductase complementary DNA from prostate4. Subsequent cloning and genetic studies showed that this gene (designated 5α-reductase 1) was normal in patients with Sor-reductase deficiency26. We report here the isolation of a second 5α-reductase cDNA by expression cloning and the polymerase chain reaction. The biochemical and pharmacological properties of this cDNA-encoded enzyme (designated 5α-reductase 2) are consistent with it being the major isozyme in genital tissue. A deletion in this gene is present in two related individuals with male pseudohermaphroditism caused by 5α-reductase deficiency. These results verify the existence of at least two 5α-reductases in man and provide insight into a fundamental hormone-mediated event in male sexual differentiation.

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    • David W. Russell

    To whom correspondence should be addressed.

Affiliations

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

    • Stefan Andersson
    • , David M. Berman
    • , Elizabeth P. Jenkins
    •  & David W. Russell

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https://doi.org/10.1038/354159a0

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