Geissler W M, Davis D L, Wu L, Bradshaw K D, Patel S, Mendonca B B, Elliston K O, Wilson J D, Russell D W, Andersson S
Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.
Nat Genet. 1994 May;7(1):34-9. doi: 10.1038/ng0594-34.
Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.
胎儿睾丸中，17β-羟基类固醇脱氢酶（17β-HSD）将雄烯二酮转化为睾酮的过程出现缺陷，会导致具有女性外生殖器的遗传男性。我们利用表达克隆技术分离出编码微粒体3型17β-HSD同工酶的cDNA，该同工酶与其他17β-HSD酶有23%的序列同一性，以NADPh作为辅因子，主要在睾丸中表达。位于9q22染色体上的17β-HSD3基因包含11个外显子。在5名无亲缘关系的男性假两性畸形患者的17β-HSD3基因中，鉴定出4个替代突变和2个剪接连接突变。这些替代突变严重损害了3型17β-HSD同工酶的活性。
