Impact of a constitutively active luteinizing hormone receptor on testicular gene expression and postnatal Leydig cell development.
Impact of a constitutively active luteinizing hormone receptor on testicular gene expression and postnatal Leydig cell development.
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DOI：
10.1016/j.mce.2008.10.016
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发表时间：
2009-01-27
影响因子：
4.1
通讯作者：
Narayan P
中科院分区：
文献类型：
--
作者：
Coonce MM;Rabideau AC;McGee S;Smith K;Narayan P
黄体生成素（LH）通过其受体（LHR）介导，在睾丸甾体形成和睾丸间质细胞分化中起着至关重要的作用。我们之前已经描述了转基因小鼠表达的基因工程，组成活性的轭式激素受体复合物（YHR），其中人绒毛膜促性腺激素（hCG）的融合蛋白共价连接到LHR。在3和5周龄表达YHR （YHR+）的雄性小鼠中，睾酮水平升高，睾丸重量下降，血清LH和FSH水平下降。在这里，我们报告了一项时间研究，以确定在出生后发育期间YHR+小鼠中表达改变的睾丸基因。3、5周龄YHR+睾丸中甾体生成酶P450 17α-羟化酶、17β-羟类固醇脱氢酶e3和5α-还原酶e1 mRNA表达水平下调。该结果与间质细胞特异性蛋白的免疫组织化学分析和间质细胞数量的定量分析相结合，确定了YHR+小鼠成年间质细胞的减少。令人惊讶的是，在WT和YHR+小鼠之间，没有检测到细胞色素P450侧链切割或类固醇急性调节蛋白RNA水平的变化。相比之下，胰岛素样生长因子结合蛋白3的mRNA水平在3和5周龄的YHR+小鼠中上调。WT和YHR+小鼠在5周龄时，几种生殖细胞特异性蛋白的mRNA水平均上调。我们的结论是，过早的高水平睾丸激素改变了一些睾丸基因的表达，损害了小鼠成年间质细胞的分化。
The actions of luteinizing hormone (LH) mediated through its receptor (LHR) are critical for testicular steroidogenesis and Leydig cell differentiation. We have previously characterized transgenic mice expressing a genetically engineered, constitutively active yoked hormone-receptor complex (YHR), in which a fusion protein of human chorionic gonadotropin (hCG) was covalently linked to LHR. Elevated testosterone levels were detected in male mice expressing YHR (YHR+) at 3 and 5 weeks of age, accompanied by decreases in testicular weight and serum levels of LH and FSH. Here we report a temporal study to identify testicular genes whose expression is altered in YHR+ mice during postnatal development. The mRNA expression levels for the steroidogenic enzymes, P450 17α-hydroxylase, 17β-hyroxysteroid dehydrogenase3 and 5α-reductase1 were down-regulated in 3 and 5 week old YHR+ testis. This result coupled with an immunohistochemical analysis of Leydig cell specific proteins and quantification of Leydig cell numbers identified a decrease in adult Leydig cells in YHR+ mice. Surprisingly, no change was detected for cytochrome P450 side-chain cleavage or steroidogenic acute regulatory protein RNA levels between WT and YHR+ mice. In contrast, mRNA levels for insulin-like growth factor binding protein 3 were up-regulated in 3 and 5 week old YHR+ mice. The mRNA levels for several germ cell-specific proteins were up-regulated at 5 weeks of age in both WT and YHR+ mice. We conclude that premature high levels of testosterone alter the expression of a select number of testicular genes and impair the differentiation of adult Leydig cells in mice.
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DOI：
10.1073/pnas.0404743101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Ma, XP;Dong, YL;Kumar, TR
通讯作者：
Kumar, TR
影响因子：
3.6
作者：
Clark, AM;Garland, KK;Russell, LD
通讯作者：
Russell, LD
影响因子：
3.5
作者：
Meehan, TP;Harmon, BG;Narayan, P
通讯作者：
Narayan, P
DOI：
10.1186/1477-7827-1-4
发表时间：
2003-02-05
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Baker, P J;Johnston, H;O'Shaughnessy, P J
通讯作者：
O'Shaughnessy, P J
影响因子：
4.8
作者：
O'Shaughnessy, PJ;Baker, P;Huhtaniemi, I
通讯作者：
Huhtaniemi, I