Genetic and pharmacological evidence for more than one human steroid 5α-reductase

Elizabeth P. Jenkins, Stefan Andersson, Julianne Imperato-McGinley, Jean D. Wilson, David W. Russell

Research output: Contribution to journalArticle

346 Citations (Scopus)

Abstract

The enzyme steroid 5α-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 5α-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDN A is normal in subjects with the genetic disease steroid 5α-reductase deficiency. We further show that in contrast to the major steroid 5a-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 5α-reductase isozymes in man.

Original languageEnglish (US)
Pages (from-to)293-300
Number of pages8
JournalJournal of Clinical Investigation
Volume89
Issue number1
StatePublished - 1992

Fingerprint

Oxidoreductases
Steroids
Pharmacology
Finasteride
Molecular Biology
Enzymes
Complementary DNA
XY Disorders of Sex Development 46
Inborn Genetic Diseases
Dihydrotestosterone
Androgens
Isoenzymes
Testosterone
Prostate
Clone Cells
Fibroblasts
Skin
Genes

Keywords

  • 4-azasteroid inhibitors
  • Androgens
  • Dihydrotestosterone
  • Isozymes
  • Pseudohermaphroditism

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Jenkins, E. P., Andersson, S., Imperato-McGinley, J., Wilson, J. D., & Russell, D. W. (1992). Genetic and pharmacological evidence for more than one human steroid 5α-reductase. Journal of Clinical Investigation, 89(1), 293-300.

Genetic and pharmacological evidence for more than one human steroid 5α-reductase. / Jenkins, Elizabeth P.; Andersson, Stefan; Imperato-McGinley, Julianne; Wilson, Jean D.; Russell, David W.

In: Journal of Clinical Investigation, Vol. 89, No. 1, 1992, p. 293-300.

Research output: Contribution to journalArticle

Jenkins, EP, Andersson, S, Imperato-McGinley, J, Wilson, JD & Russell, DW 1992, 'Genetic and pharmacological evidence for more than one human steroid 5α-reductase', Journal of Clinical Investigation, vol. 89, no. 1, pp. 293-300.
Jenkins, Elizabeth P. ; Andersson, Stefan ; Imperato-McGinley, Julianne ; Wilson, Jean D. ; Russell, David W. / Genetic and pharmacological evidence for more than one human steroid 5α-reductase. In: Journal of Clinical Investigation. 1992 ; Vol. 89, No. 1. pp. 293-300.
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