Role of activin, follistatin, and inhibin in the regulation of Kiss-1 gene expression in hypothalamic cell models.
Role of activin, follistatin, and inhibin in the regulation of Kiss-1 gene expression in hypothalamic cell models.
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激活素、卵泡抑素和抑制素在下丘脑细胞模型中 Kiss-1 基因表达调节中的作用。
DOI：
10.1093/biolre/ioz094
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发表时间：
2019
影响因子：
3.6
通讯作者：
Kyo S.
中科院分区：
文献类型：
--
作者：
Tumurgan Z;Kanasaki H;Tumurbaatar T;Oride A;Okada H;Hara T;Kyo S.
下丘脑弓状核（ARC）中的Kisspeptin（由Kiss-1基因编码）通过调节促性腺激素释放激素（GnRH）的脉冲式释放来支配下丘脑-垂体-性腺（HPG）轴。同时，kisspeptin在前腹侧室周核（AVPV）区域已牵连在雌二醇（E2）诱导的GnRH浪涌。表达Kiss-1的细胞模型mHypoA-55在ARC区表现出Kiss-1神经元的特征。另一方面，表达Kiss-1的mHypoA-50细胞来源于AVPV区域。在mHypoA-55 ARC细胞中，激活素显著增加Kiss-1基因表达。单独的卵泡抑素降低了这些细胞内Kiss-1的表达。有趣的是，激活素诱导的Kiss-1基因表达被卵泡抑素完全消除。抑制素A，但不是抑制素B降低Kiss-1表达。激活素增加的Kiss-1表达也可被白藜芦醇A消除。用卵泡抑素或卵泡抑素A预处理细胞显著抑制mHypoA-55细胞中kisspeptin或GnRH诱导的Kiss-1基因表达。相比之下，在mHypoA-50 AVPV细胞模型中，激活素、卵泡抑素和卵泡抑素A不调节Kiss-1基因表达。组成激活素和卵泡抑素的亚基以及卵泡抑素在mHypoA-55和mHypoA-50细胞中表达。mHypoA-55 ARC细胞中卵泡抑素和卵泡抑素βA、βB亚基的表达明显增高。此外，我们还发现，在mHypoA-55 ARC细胞中，E2的存在可调节卵泡抑素和卵泡素抑制素α亚基基因的表达。这项研究的结果表明，ARC区域内的激活素，卵泡抑素，和E2的影响下，参与HPG轴的调节。
Kisspeptin (encoded by the Kiss-1 gene) in the arcuate nucleus (ARC) of the hypothalamus governs the hypothalamic-pituitary-gonadal (HPG) axis by regulating pulsatile release of gonadotropin-releasing hormone (GnRH). Meanwhile, kisspeptin in the anteroventral periventricular nucleus (AVPV) region has been implicated in estradiol (E2)-induced GnRH surges. Kiss-1–expressing cell model mHypoA-55 exhibits characteristics of Kiss-1 neurons in the ARC region. On the other hand, Kiss-1 expressing mHypoA-50 cells originate from the AVPV region. In the mHypoA-55 ARC cells, activin significantly increased Kiss-1 gene expression. Follistatin alone reduced Kiss-1 expression within these cells. Interestingly, activin-induced Kiss-1 gene expression was completely abolished by follistatin. Inhibin A, but not inhibin B reduced Kiss-1 expression. Activin-increased Kiss-1 expression was also abolished by inhibin A. Pretreatment of the cells with follistatin or inhibin A significantly inhibited kisspeptin- or GnRH-induced Kiss-1 gene expression in mHypoA-55 cells. In contrast, in the mHypoA-50 AVPV cell model, activin, follistatin, and inhibin A did not modulate Kiss-1 gene expression. The subunits that compose activin and inhibin, as well as follistatin were expressed in both mHypoA-55 and mHypoA-50 cells. Expression of inhibin βA and βB subunits and follistatin was much higher in mHypoA-55 ARC cells. Furthermore, we found that expression of the inhibin α subunit and follistatin genes was modulated in the presence of E2 in mHypoA-55 ARC cells. The results of this study suggest that activin, follistatin, and inhibin A within the ARC region participate in the regulation of the HPG axis under the influence of E2.