1 Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan.
2 Laboratory of Integrative Brain Science, Department of Biology, Waseda University and Center for Medical Life Science of Waseda University, Tokyo, Japan.
Reprod Sci. 2019 Sep;26(9):1249-1255. doi: 10.1177/1933719118813456. Epub 2018 Nov 20.
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.
Kisspeptin，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 显示出小鼠下丘脑前腹内脑室（AVPV）区域神经元细胞的特征。由于这些细胞中的 Kiss-1 基因表达受雌激素（E2）上调，因此 mHypoA-50 细胞被认为是研究 AVPV 区域 Kiss-1 表达神经元的有价值模型。这些细胞还表达 RFamide 相关肽-3（RFRP-3），这是促性腺激素抑制激素的哺乳动物同源物。褪黑素刺激增加了 mHypoA-50 细胞中的 RFRP-3 表达。此外，E2 刺激增加了这些细胞中 RFRP-3 的表达。用外源性 RFRP-3 处理 mHypoA-50 细胞会导致细胞内 Kiss-1 信使 RNA 表达增加；然而，RFRP-3 不会改变这些细胞中促性腺激素释放激素或 kisspeptin 诱导的 Kiss-1 基因表达。此外，我们发现 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 mHypoA-50 细胞中 E2 诱导的正反馈。我们的观察表明，RFRP-3 可能通过直接或间接增加 Kiss-1 基因表达参与正反馈调节。
