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

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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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  1. David W. Russell: To whom correspondence should be addressed.

Authors and 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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  1. Stefan Andersson
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  2. David M. Berman
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  3. Elizabeth P. Jenkins
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  4. David W. Russell
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Andersson, S., Berman, D., Jenkins, E. et al. Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism. Nature 354, 159–161 (1991). https://doi.org/10.1038/354159a0

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

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