Yagi Hiroko, Kageyama Kazunori, Kinoshita Noriko, Niioka Kanako, Yamagata Satoshi, Ito Etsuro, Daimon Makoto
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan; Department of Pediatrics, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
Neurosci Lett. 2019 Jan 23;692:137-142. doi: 10.1016/j.neulet.2018.11.009. Epub 2018 Nov 6.
The ancestral insulin/relaxin peptide superfamily member relaxin-3 is an important regulator of food intake and behaviors related to anxiety and motivation. Relaxin family peptide receptor 1 (RXFP1) and RXFP3 are expressed in the rat hypothalamic paraventricular nucleus (PVN). Corticotropin-releasing factor (CRF) is produced in the PVN in response to stressors and promotes adrenocorticotropic hormone secretion from the anterior pituitary. We hypothesized that relaxin-3 directly regulates Crf expression in the hypothalamus and investigated its effect on Crf expression in cultured hypothalamic 4B cells. Relaxin-3 increased Crf mRNA levels and stimulated Crf promoter activity. Both protein kinase A and C pathways contributed to relaxin-3-induced Crf promoter activity. Rxfp1 and Rxfp3 mRNA and their proteins were expressed in cultured hypothalamic 4B cells. Relaxin-3 decreased Rxfp1 mRNA and protein levels and increased Rxfp3 mRNA and protein levels. These results suggested that the action of relaxin-3 in cultured hypothalamic 4B cells may be regulated through both RXFP1 and RXFP3.
胰岛素/松弛素肽超家族的原始成员松弛素-3是食物摄入以及与焦虑和动机相关行为的重要调节因子。松弛素家族肽受体1（RXFP1）和RXFP3在大鼠下丘脑室旁核（PVN）中表达。促肾上腺皮质激素释放因子（CRF）在PVN中产生以应对应激源，并促进垂体前叶促肾上腺皮质激素的分泌。我们假设松弛素-3直接调节下丘脑Crf的表达，并研究了其对培养的下丘脑4B细胞中Crf表达的影响。松弛素-3增加了Crf mRNA水平并刺激了Crf启动子活性。蛋白激酶A和C途径均有助于松弛素-3诱导的Crf启动子活性。Rxfp1和Rxfp3 mRNA及其蛋白在培养的下丘脑4B细胞中表达。松弛素-3降低了Rxfp1 mRNA和蛋白水平，并增加了Rxfp3 mRNA和蛋白水平。这些结果表明，松弛素-3在培养的下丘脑4B细胞中的作用可能通过RXFP1和RXFP3两者来调节。
