Thigpen A E, Silver R I, Guileyardo J M, Casey M L, McConnell J D, Russell D W
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
J Clin Invest. 1993 Aug;92(2):903-10. doi: 10.1172/JCI116665.
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.
二氢睾酮的合成由类固醇5α-还原酶同工酶催化，分为1型和2型。2型同工酶的突变会导致男性假两性畸形，患病男性出生时外生殖器在表型上为女性。这种疾病有两个显著且无法解释的特征：患病男性的外生殖器在青春期会发生男性化，且这些个体的颞部毛发脱落较少。通过免疫印迹法研究了5α-还原酶同工酶的组织特异性和发育表达模式。1型同工酶在胎儿中无法检测到，在新生儿皮肤和头皮中短暂表达，并从青春期开始在皮肤中永久表达。成年秃发头皮与非秃发头皮之间的5α-还原酶1型表达没有质的差异。2型同工酶在新生儿的皮肤和头皮中短暂表达。2型是在胎儿生殖器皮肤、男性附属性腺以及前列腺（包括良性前列腺增生和前列腺腺癌组织）中可检测到的主要同工酶。两种同工酶都在肝脏中表达，但仅在出生后。这些结果与1型5α-还原酶在青春期负责2型缺陷受试者的男性化一致，并表明2型同工酶可能是男性型秃发发展的起始因素。
