Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression.

TLDR

Dihydrotestosterone synthesis is catalyzed by steroid 5α‑reductase isozymes 1 and 2, and mutations in type 2 cause male pseudohermaphroditism with virilization at puberty and reduced hair regression. The study examined tissue‑specific and developmental expression of the two isozymes using immunoblotting. Type 1 is absent in the fetus, appears transiently in newborn skin, and persists from puberty onward, while type 2 is transient in newborn skin, dominates fetal genital skin and male accessory glands, and is present in prostate tissues; both are expressed in the liver after birth, suggesting type 1 mediates virilization in type 2‑deficient individuals and type 2 may initiate male pattern baldness.

Abstract

The synthesis of dihydrotestosterone is catalyzed by steroid 5 alpha-reductase isozymes, designated types 1 and 2. Mutation of type 2 results in male pseudohermaphroditism, in which the external genitalia are phenotypically female at birth. Two striking and unexplained features of this disorder are that external genitalia of affected males undergo virilization during puberty and that these individuals have less temporal hair regression. The tissue-specific and developmental expression patterns of the 5 alpha-reductase isozymes were investigated by immunoblotting. The type 1 isozyme is not detectable in the fetus, is transiently expressed in newborn skin and scalp, and permanently expressed in skin from the time of puberty. There was no qualitative difference in 5 alpha-reductase type 1 expression between adult balding vs. nonbalding scalp. The type 2 isozyme is transiently expressed in skin and scalp of newborns. Type 2 is the predominant isozyme detectable in fetal genital skin, male accessory sex glands, and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues. Both isozymes are expressed in the liver, but only after birth. These results are consistent with 5 alpha-reductase type 1 being responsible for virilization in type 2-deficient subjects during puberty, and suggest that the type 2 isozyme may be an initiating factor in development of male pattern baldness.