Genetic and pharmacological evidence for more than one human steroid 5 alpha-reductase.
The enzyme steroid 5 alpha-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 5 alpha-reductase enzyme. Here, we report molecular and genetic studies demonstrating that the gene encoding this cDNA is normal in subjects with the genetic disease steroid 5 alpha-reductase deficiency. We further show that in contrast to the major steroid 5 alpha-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 5 alpha-reductase isozymes in man.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
E P
EP
Jenkins
S
S
Andersson
J
J
Imperato-McGinley
J D
JD
Wilson
D W
DW
Russell
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004277:DNA, Single-Stranded; D013196:Dihydrotestosterone / Q000378:metabolism; D012734:Disorders of Sex Development / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011467:Prostate / Q000166:cytology / Q000201:enzymology; D012867:Skin / Q000166:cytology / Q000201:enzymology; D013739:Testosterone / Q000378:metabolism
D004277:DNA, Single-Stranded; D007527:Isoenzymes; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase