Ieda Nahoko, Kawai Narumi, Ishii Hirotaka, Ihara Kunio, Inoue Naoko, Uenoyama Yoshihisa, Tsukamura Hiroko
Graduate School of Bioagricultural Sciences Nagoya University Nagoya Japan.
Department of Anatomy and Neurobiology Nippon Medical School Tokyo Japan.
Reprod Med Biol. 2018 Mar 11;17(2):164-172. doi: 10.1002/rmb2.12085. eCollection 2018 Apr.
Hypothalamic kisspeptin neurons are considered to play a critical role in regulating mammalian reproduction and integrating humoral and neuronal inputs that control gonadotropin-releasing hormone (GnRH)/gonadotropin release. The present study aimed to investigate the upstream regulator candidates for kisspeptin neurons.
Visualized kisspeptin neurons that were taken from the arcuate nucleus (ARC) of -tdTomato rats were subjected to next-generation sequencing (NGS) analysis. In situ hybridization (ISH) for the calcitonin receptor gene () was performed throughout the whole forebrain of ovariectomized wild-type female rats that had been implanted with a negative feedback level of estrogen, because the expression was evident in the ARC kisspeptin neurons from the NGS analysis. Then, a double ISH was performed for the and kisspeptin gene () in the brain regions, containing either the anteroventral periventricular nucleus (AVPV) or ARC of the female rats.
The NGS analysis revealed that the was highly expressed in the ARC kisspeptin neurons. It was found that the was co-expressed in 12% and 22% of the -expressing cells in the ARC and AVPV, respectively.
The present study suggests that calcitonin receptor signaling could be involved in the regulation of reproductive function through the direct control of the ARC and/or AVPV kisspeptin neurons, and then GnRH/gonadotropin release.
下丘脑促性腺激素释放激素神经元被认为在调节哺乳动物繁殖以及整合控制促性腺激素释放激素（GnRH）/促性腺激素释放的体液和神经元输入方面发挥关键作用。本研究旨在探究促性腺激素释放激素神经元的上游调节因子候选物。
对取自-tdTomato大鼠弓状核（ARC）的可视化促性腺激素释放激素神经元进行下一代测序（NGS）分析。对已植入雌激素负反馈水平的去卵巢野生型雌性大鼠的整个前脑进行降钙素受体基因（）的原位杂交（ISH），因为从NGS分析中发现该基因在ARC促性腺激素释放激素神经元中表达明显。然后，对雌性大鼠的包含室旁前腹核（AVPV）或ARC的脑区进行该基因和促性腺激素释放激素基因（）的双重ISH。
NGS分析显示该基因在ARC促性腺激素释放激素神经元中高表达。发现在ARC和AVPV中分别有12%和22%的表达该基因的细胞共表达该基因。
本研究表明降钙素受体信号可能通过直接控制ARC和/或AVPV促性腺激素释放激素神经元，进而调节GnRH/促性腺激素释放，参与生殖功能的调节。
