TISSUE DISTRIBUTION AND ONTOGENY OF STEROID 5-ALPHA-REDUCTASE ISOZYME EXPRESSION

TISSUE DISTRIBUTION AND ONTOGENY OF STEROID 5-ALPHA-REDUCTASE ISOZYME EXPRESSION
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DOI:
10.1172/jci116665
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发表时间:
1993-08-01
影响因子:
15.9
通讯作者:
RUSSELL, DW
RUSSELL, DW
中科院分区:
医学1区
文献类型:
--
作者:
THIGPEN, AE;SILVER, RI;RUSSELL, DW

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双氢睾酮的合成由类固醇5 α-还原酶同工酶催化,命名为1型和2型。2型突变导致男性假两性畸形,其中外生殖器在出生时表现为女性。这种疾病的两个突出和无法解释的特点是,受影响的男性的外生殖器在青春期经历男性化,这些人有较少的颞部毛发退化。5 α-还原酶同工酶的组织特异性和发育的表达模式进行了研究,通过免疫印迹。1型同工酶在胎儿中检测不到,在新生儿皮肤和头皮中短暂表达,从青春期开始在皮肤中永久表达。有没有5 α-还原酶1型成人秃头与非秃头头皮之间的表达质的差异。2型同工酶在新生儿皮肤和头皮中瞬时表达。2型是在胎儿生殖器皮肤、男性附性腺和前列腺(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。这两种同工酶都在肝脏中表达,但仅在出生后表达。这些结果是一致的5 α-还原酶1型负责男性化2型缺陷的受试者在青春期,并建议2型同工酶可能是一个启动因素,在发展中的男性型秃发。
The synthesis of dihydrotestosterone is catalyzed by steroid 5alpha-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 5alpha-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 5alpha-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 5alpha-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.