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 is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Wilson, J. D. Harvey Lect. 79, 145–172 (1985).
Wilson, J. D. Endocrinology 25, 491–508 (1975).
Griffin, J. E. & Wilson, J. D. in The Metabolic Basis of Inherited Disease (eds Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D.) 1919–1944 (McGraw-Hill, New York, 1989).
Andersson, S. & Russell, D. W. Proc. natn. Acad. Sci. U.S.A. 87, 3640–3644 (1990).
Andersson, S., Davis, D., Dahlbäck, Jölrnvall, H. & Russell, D. W. J. biol Chem. 264, 8222–8229 (1989).
Andersson, S., Bishop, R. W. & Russell, D. W. J. biol. Chem. 264, 16249–16255 (1989).
Saiki, R. K. et al. Science 239, 487–491 (1988).
Shinozaki, K. et al. EMBO J. 5, 2043–2049 (1986).
Rassart, E., Nelbach, L. & Jolicoeur, P. J. Virol. 60, 910–919 (1986).
Laux, G., Perricaudet, M. & Farrell, P. J. EMBO J. 7, 769–774 (1988).
Moore, R. J., Griffin, J. E. & Wilson, J. D. J. biol. Chem. 250, 7168–7172 (1975).
Liang, T., Cascieri, M. A., Cheung, A. H., Reynolds, G. F. & Rasmusson, G. H. Endocrinology 117, 571–579 (1985).
George, F. W., Russell, D. W. & Wilson, J. D. Proc. natn. Acad. Sci. U.S.A. 88, 8044–8047 (1991).
Brooks, J. R. et al. Endocrinology 109, 830–836 (1981).
Vermeulen, A., Giagulli, V. A., DeSchepper, P., Buntinx, A. & Stoner, E. Prostate 14, 45–53 (1989).
Moore, R. J. & Wilson, J. D. J. biol. Chem. 251, 5895–5900 (1976).
Imperato-McGinley, J., et al. Clin. Endocrin. 34, 293–298 (1991).
Hobbs, H. H., Russell, D. W., Brown, M. S. & Goldstein, J. L. A. Rev. Genet. 24, 133–170 (1990).
Horovitz, H. R. & Sternberg, P. W. Nature 351, 535–541 (1991).
Sambrook, J., Fritsch, E. F. & Maniatis, T. in Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory. Cold Spring Harbor. New York, 1989).
Gorman, C. M., Gies, D. R. & McCray, G. DNA Prot. Engng. Tech. 2, 3–10 (1990).
Strathmann, M., Wilkie, T. M. & Simon, M. I. Proc. natn. Acad. Sci. U.S.A. 85, 7407–7409 (1989).
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).
Lehrman, M. A. et al. Science 227, 140–146 (1985).
Church, G. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 81, 1991–1995 (1984).
Jenkins, E. P., Andersson, S., Imperato-McGinley, J., Wilson, J. D. & Russell, D. W. J. clin. Invest. (in the press).
Herskowitz, I. Nature 342, 749–757 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/354159a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.