Liver receptor homologue-1 regulates gonadotrope function.
Liver receptor homologue-1 regulates gonadotrope function.
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DOI：
10.1677/jme.1.00001
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发表时间：
2007-02
影响因子：
3.5
通讯作者：
Weiming Zheng;Jingying Yang;Qiaorong Jiang;Zhibin He;L. Halvorson
中科院分区：
文献类型：
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作者：
Weiming Zheng;Jingying Yang;Qiaorong Jiang;Zhibin He;L. Halvorson
在过去的十年中，我们对调节促性腺激素基因表达的转录因子的理解取得了重大进展。这些因子中最重要的因子之一，类固醇生成因子-1（SF-1; NR 5A 1）对促性腺激素和GnRH受体表达至关重要。有趣的是，一个密切相关的核激素受体，肝受体同源物-1（LRH-1; NR 5A 2）最近已被检测到在垂体前叶;然而，其功能意义在这个组织中还没有被调查。对于这里报道的实验，我们假设LRH-1在促性腺激素生理学中起着以前未被认识的作用。为此，我们首先证明了LRH-1 mRNA和蛋白质表达的原代垂体细胞和促性腺激素衍生的细胞系。我们接下来表明，LRH-1刺激促性腺激素释放激素受体和促性腺激素亚单位基因的启动子活性。在LH β基因内，这种反应似乎是由DNA结合和反式激活介导的，通过先前表征的SF-1顺式元件。据我们所知，这是第一份报告表明LRH-1在垂体前叶促性腺激素人群中的功能作用。
Over the past decade, substantial advances have been made in our understanding of the transcription factors which regulate gene expression in gonadotropes. One of the most important of these factors, steroidogenic factor-1 (SF-1; NR5A1) is critical for gonadotropin and GnRH-receptor expression. Interestingly, a closely related nuclear hormone receptor, liver receptor homologue-1 (LRH-1; NR5A2) has recently been detected in the anterior pituitary gland; however, its functional significance in this tissue has not been investigated. For the experiments reported here, we hypothesized that LRH-1 plays a previously unrecognized role in gonadotrope physiology. Towards this end, we first demonstrate LRH-1 mRNA and protein expression in both primary pituitary cells and gonadotrope-derived cell lines. We next show that LRH-1 stimulates promoter activity of the GnRH-receptor and gonadotropin subunit genes. Within the LHbeta gene, this response appears to be mediated by DNA-binding and transactivation through previously characterized SF-1 cis-elements. To our knowledge, this is the first report demonstrating a functional role for LRH-1 in the gonadotrope population of the anterior pituitary gland.