Deletion of steroid 5α-reductase 2 gene in male pseudohermaphroditism
- 14 November 1991
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 354 (6349), 159-161
- https://doi.org/10.1038/354159a0
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.This publication has 29 references indexed in Scilit:
- Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase.Proceedings of the National Academy of Sciences of the United States of America, 1991
- Multiple intercellular signalling systems control the development of the Caenorhabditis elegans vulvaNature, 1991
- A cluster of male pseudohermaphrodites with 5α‐reductase deficiency in Papua New GuineaClinical Endocrinology, 1991
- THE LDL RECEPTOR LOCUS IN FAMILIAL HYPERCHOLESTEROLEMIA: Mutational Analysis of a Membrane ProteinAnnual Review of Genetics, 1990
- Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases.Proceedings of the National Academy of Sciences of the United States of America, 1990
- A regulatory hierarchy for cell specialization in yeastNature, 1989
- Diversity of the G-protein family: sequences from five additional alpha subunits in the mouse.Proceedings of the National Academy of Sciences of the United States of America, 1989
- Hormonal effects of an orally active 4‐azasteroid inhibitor of 5α‐reductase in humansThe Prostate, 1989
- Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA PolymeraseScience, 1988
- Genomic sequencing.Proceedings of the National Academy of Sciences of the United States of America, 1984