Role of RFRP-3 in the Regulation of Kiss-1 Gene Expression in the AVPV Hypothalamic Cell Model mHypoA-50
Role of RFRP-3 in the Regulation of Kiss-1 Gene Expression in the AVPV Hypothalamic Cell Model mHypoA-50
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DOI：
10.1177/1933719118813456
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发表时间：
2019-09-01
影响因子：
2.9
通讯作者：
Kyo, Satoru
中科院分区：
文献类型：
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作者：
Kanasaki, Haruhiko;Tumurbaatar, Tuvshintugs;Kyo, Satoru
Kispeptin由Kiss-1基因编码，通过调节下丘脑-垂体-性腺轴在生殖功能中发挥关键作用。最近建立的Kiss-1表达细胞模型mHypoA-50显示了小鼠下丘脑前腹侧脑室周围区(AVPV)神经细胞的特征。由于雌激素上调Kiss-1基因在这些细胞中的表达，mHypoA-50细胞被认为是研究AVPV区Kiss-1表达神经元的有价值的模型。这些细胞还表达RFamide相关肽-3(RFRP-3)，这是一种促性腺激素抑制激素的哺乳动物同源物。褪黑素刺激可增加mHypoA-50细胞中RFRP-3的表达。此外，E2刺激增加了这些细胞中RFRP-3的表达。外源性RFRP-3处理mHypoA-50细胞后，细胞内Kiss-1信使RNA表达增加，但不影响促性腺激素释放激素或Kispeptin诱导的Kiss-1基因表达。此外，我们还发现，RFRP-3刺激增加了促肾上腺皮质激素释放激素的表达，这可能参与了E2诱导的mHypoA-50细胞的正反馈。我们的观察表明，RFRP-3可能通过直接或间接增加Kiss-1基因的表达而参与正反馈调节。
Kisspeptin, encoded by the Kiss-1 gene, plays a crucial role in reproductive function by governing the hypothalamic-pituitary-gonadal axis. The recently established Kiss-1-expressing cell model mHypoA-50 displays characteristics of neuronal cells of the anteroventral periventricular (AVPV) region of the mouse hypothalamus. Because Kiss-1 gene expression in these cells is upregulated by estradiol (E2), mHypoA-50 cells are regarded as a valuable model for the study of Kiss-1-expressing neurons in the AVPV region. These cells also express RFamide-related peptide-3 (RFRP-3), a mammalian homolog of gonadotropin inhibitory hormone. The RFRP-3 expression in mHypoA-50 cells was increased by melatonin stimulation. In addition, E2 stimulation increased RFRP-3 expression in these cells. Treatment of the mHypoA-50 cells with exogenous RFRP-3 resulted in the increase of Kiss-1 messenger RNA expression within the cells; however, RFRP-3 did not modify gonadotropin-releasing hormone or kisspeptin-induced Kiss-1 gene expression in these cells. In addition, we found that RFRP-3 stimulation increased the expression of corticotropin-releasing hormone, which may be involved in E2-induced positive feedback in mHypoA-50 cells. Our observations suggest that RFRP-3 might be involved in positive feedback regulation by directly or indirectly increasing Kiss-1 gene expression.