Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and the androgen receptor
Tissue-specific transcription profiles of sex steroid biosynthesis enzymes and the androgen receptor
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DOI：
10.1007/s00109-006-0049-1
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发表时间：
2006-08-01
影响因子：
4.7
通讯作者：
Hiort, O.
中科院分区：
文献类型：
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作者：
Hoppe, U.;Holterhus, P. -M.;Hiort, O.
17 β-羟基类固醇脱氢酶（17 β-HSD）和5 α-还原酶同工酶在性类固醇的形成和代谢中起着至关重要的作用。不仅关键的雄激素睾酮和双氢睾酮，而且其前体也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。本研究的目的是相对定量17 β-HSD同工酶，即1，2，3，4，5，7和10型，连同5 α-还原酶1型和2型，和受体在正常人男性和女性的mRNA的表达。从两种性别的外周血细胞和从表型正常男性获得的两种不同定位（包皮和阴囊皮肤）的生殖器皮肤成纤维细胞（GSF）中分离RNA。通过使用LightCycler仪器（Roche）的定量逆转录酶聚合酶链反应对mRNA表达进行半定量。所检查的酶在血液和GSF RNA样品之间的转录模式中显示出统计学显著差异。在GSF样品中，在17 β-HSD 1、2、4和5型以及雄激素受体的转录中，两种检查的定位之间也存在显著差异。我们发现在所有调查组织中酶转录模式的个体间差异很大。在外周血细胞中，未观察到性别特异性差异。我们的结论是，性类固醇酶不仅在生殖器原发性靶组织中表达，而且在外周血中也表达。在不同靶组织中的表达可能有助于人类个体性和组织特异性表型。
17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 5 alpha-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 17 beta-HSD isoenzymes, namely, type 1, 2, 3, 4, 5, 7, and 10, together with the 5 alpha-reductase type 1 and 2, and the 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 17 beta-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.