TY - JOUR
T1 - Genetic and pharmacological evidence for more than one human steroid 5α-reductase
AU - Jenkins, Elizabeth P.
AU - Andersson, Stefan
AU - Imperato-McGinley, Julianne
AU - Wilson, Jean D.
AU - Russell, David W.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - 4-azasteroid inhibitors
KW - Androgens
KW - Dihydrotestosterone
KW - Isozymes
KW - Pseudohermaphroditism
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M3 - Article
C2 - 1345916
AN - SCOPUS:0026543274
SN - 0021-9738
VL - 89
SP - 293
EP - 300
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 1
ER -