Hoppe U, Holterhus P-M, Wünsch L, Jocham D, Drechsler T, Thiele S, Marschke C, Hiort O
Department of Pediatrics and Adolescent Medicine, University of Lübeck, Lübeck, Germany.
J Mol Med (Berl). 2006 Aug;84(8):651-9. doi: 10.1007/s00109-006-0049-1. Epub 2006 Mar 25.
17beta-hydroxysteroid dehydrogenase (17beta-HSD) and 5alpha-reductase isoenzymes play a crucial role in the formation and metabolism of sex steroids. Not only the key androgens testosterone and dihydrotestosterone but also their precursors are potent activators of the androgen receptor and are, therefore, likely to act as determinants of male sexual differentiation and maturation in a differentially regulated way. The aim of the present study was to relatively quantify the expression of the mRNA of 17beta-HSD isoenzymes, namely, type 1, 2, 3, 4, 5, 7, and 10, together with the 5alpha-reductase type 1 and 2, and the androgen receptor in normal human males and females. RNA was isolated from peripheral blood cells of both sexes and from genital skin fibroblasts (GSFs) of two different localizations (foreskin and scrotal skin) obtained from phenotypically normal males. mRNA expression was semi-quantified by quantitative reverse-transcriptase polymerase chain reaction with the LightCycler Instrument (Roche). The examined enzymes show statistically significant differences in their transcription pattern between the blood and the GSF RNA samples. Within the GSF samples, there are also significant variations between the two examined localizations in the transcription of 17beta-HSD type 1, 2, 4, and 5 as well as for the androgen receptor. We found large interindividual variation of enzyme transcription patterns in all investigated tissues. In peripheral blood cells, no sex-specific differences were seen. We conclude that sex steroid enzymes are expressed not only in genital primary target tissues but also in peripheral blood. The expression in different target tissues may contribute to both the individual sexual and tissue-specific phenotype in humans.
17β-羟基类固醇脱氢酶(17β-HSD)和5α-还原酶同工酶在性类固醇的形成和代谢中起关键作用。不仅关键雄激素睾酮和双氢睾酮,而且它们的前体都是雄激素受体的有效激活剂,因此,可能以差异调节的方式作为男性性分化和成熟的决定因素。本研究的目的是比较定量17β-HSD同工酶(即1型、2型、3型、4型、5型、7型和10型)、5α-还原酶1型和2型以及雄激素受体在正常男性和女性中的mRNA表达。从两性的外周血细胞以及从表型正常男性获得的两个不同部位(包皮和阴囊皮肤)的生殖器皮肤成纤维细胞(GSF)中分离RNA。使用LightCycler仪器(罗氏公司)通过定量逆转录聚合酶链反应对mRNA表达进行半定量。所检测的酶在血液和GSF RNA样本之间的转录模式上显示出统计学上的显著差异。在GSF样本中,17β-HSD 1型、2型、4型和5型以及雄激素受体的转录在两个检测部位之间也存在显著差异。我们发现在所有研究的组织中酶转录模式存在较大个体差异。在外周血细胞中,未观察到性别特异性差异。我们得出结论,性类固醇酶不仅在生殖器主要靶组织中表达,而且在外周血中也有表达。在不同靶组织中的表达可能有助于人类个体的性特征和组织特异性表型。