Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse
Differential regulation of KiSS-1 mRNA expression by sex steroids in the brain of the male mouse
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DOI：
10.1210/en.2005-0323
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Steiner, RA
中科院分区：
文献类型：
--
作者：
Smith, JT;Dungan, HM;Steiner, RA
Kisspeptins是Kiss 1基因的产物，与G蛋白偶联受体GPR 54结合。Kisspeptins和GPR 54参与GnRH分泌的神经内分泌调节。为了验证睾酮调节Kiss 1基因表达的假设，我们比较了完整、去势和去势/睾酮（T）处理雄性小鼠组中KiSS-1 mRNA的表达。在弓状核（Arc）中，去势导致KiSS-1 mRNA表达显著增加，而T替代完全逆转，而在前腹侧室周核中，结果相反，即去势降低KiSS-1 mRNA表达，T增加KiSS-1 mRNA表达。在弧中，T对KiSS-1 mRNA的影响完全模仿雌激素，但只有部分模仿双氢睾酮，nonaromatizable雄激素，这表明雌激素受体（ER）和雄激素受体（AR）发挥作用，T介导的KiSS-1的调节。T对ER α缺失或AR亚型等位基因缺失小鼠KiSS-1表达的影响研究表明，T的作用由ER α和AR途径介导，这一点通过Arc中大多数KiSS-1神经元中ER α或AR共表达的存在得到证实。这些观察结果表明，KiSS-1神经元在弧，其转录活性被T抑制，GnRH分泌的负反馈调节的目标，而KiSS-1神经元在前腹侧室周核，其活性被T刺激，可能介导其他T依赖性过程。
Kisspeptins are products of the Kiss1 gene, which bind to GPR54, a G protein-coupled receptor. Kisspeptins and GPR54 have been implicated in the neuroendocrine regulation of GnRH secretion. To test the hypothesis that testosterone regulates Kiss1 gene expression, we compared the expression of KiSS-1 mRNA among groups of intact, castrated, and castrated/ testosterone ( T)-treated male mice. In the arcuate nucleus ( Arc), castration resulted in a significant increase in KiSS-1 mRNA, which was completely reversed with T replacement, whereas in the anteroventral periventricular nucleus, the results were the opposite, i.e. castration decreased and T increased KiSS-1 mRNA expression. In the Arc, the effects of T on KiSS-1 mRNA were completely mimicked by estrogen but only partially mimicked by dihydrotestosterone, a nonaromatizable androgen, suggesting that both estrogen receptor ( ER) and androgen receptor (AR) play a role in T-mediated regulation of KiSS-1. Studies of the effects of T on KiSS-1 expression in mice with either a deletion of the ER alpha or a hypomorphic allele to the AR revealed that the effects of T are mediated by both ER alpha and AR pathways, which was confirmed by the presence of either ER alpha or AR coexpression in most KiSS-1 neurons in the Arc. These observations suggest that KiSS-1 neurons in the Arc, whose transcriptional activity is inhibited by T, are targets for the negative feedback regulation of GnRH secretion, whereas KiSS-1 neurons in the anteroventral periventricular nucleus, whose activity is stimulated by T, may mediate other T-dependent processes.