Department of Reproductive Medicine, University of California San Diego, La Jolla, CA, USA.
J Neuroendocrinol. 2013 Oct;25(10):876-86. doi: 10.1111/jne.12084.
The neuropeptides kisspeptin (encoded by Kiss1) and RFamide-related peptide-3 (also known as GnIH; encoded by Rfrp) are potent stimulators and inhibitors, respectively, of reproduction. Whether kisspeptin or RFRP-3 might act directly on each other's neuronal populations to indirectly modulate reproductive status is unknown. To examine possible interconnectivity of the kisspeptin and RFRP-3 systems, we performed double-label in situ hybridisation (ISH) for the RFRP-3 receptors, Gpr147 and Gpr74, in hypothalamic Kiss1 neurones of adult male and female mice, as well as double-label ISH for the kisspeptin receptor, Kiss1r, in Rfrp-expressing neurones of the hypothalamic dorsal-medial nucleus (DMN). Only a very small proportion (5-10%) of Kiss1 neurones of the anteroventral periventricular region expressed Gpr147 or Gpr74 in either sex, whereas higher co-expression (approximately 25%) existed in Kiss1 neurones in the arcuate nucleus. Thus, RFRP-3 could signal to a small, primarily arcuate, subset of Kiss1 neurones, a conclusion supported by the finding of approximately 35% of arcuate kisspeptin cells receiving RFRP-3-immunoreactive fibre contacts. By contrast to the former situation, no Rfrp neurones co-expressed Kiss1r in either sex, and Tacr3, the receptor for neurokinin B (NKB; a neuropeptide co-expressed with arcuate kisspeptin neurones) was found in <10% of Rfrp neurones. Moreover, kisspeptin-immunoreactive fibres did not readily appose RFRP-3 cells in either sex, further excluding the likelihood that kisspeptin neurones directly communicate to RFRP-3 neurones. Lastly, despite abundant NKB in the DMN region where RFRP-3 soma reside, NKB was not co-expressed in the majority of Rfrp neurones. Our results suggest that RFRP-3 may modulate a small proportion of kisspeptin-producing neurones in mice, particularly in the arcuate nucleus, whereas kisspeptin neurones are unlikely to have any direct reciprocal actions on RFRP-3 neurones.
神经肽 kisspeptin（由 Kiss1 编码）和 RFamide 相关肽-3（也称为 GnIH；由 Rfrp 编码）分别是生殖的有力刺激物和抑制剂。 kisspeptin 或 RFRP-3 是否可能直接作用于彼此的神经元群体，从而间接调节生殖状态尚不清楚。为了研究 kisspeptin 和 RFRP-3 系统之间可能的连通性，我们对成年雄性和雌性小鼠下丘脑 Kiss1 神经元中的 RFRP-3 受体 Gpr147 和 Gpr74 进行了双重标记原位杂交（ISH），以及对下丘脑背内侧核（DMN）中表达 Rfrp 的神经元中的 kisspeptin 受体 Kiss1r 进行了双重标记 ISH。在两性中，仅有一小部分（5-10%）前腹侧室周区的 Kiss1 神经元表达 Gpr147 或 Gpr74，而在弓状核中存在更高的共表达（约 25%）。因此，RFRP-3 可以向一小部分主要位于弓状核的 Kiss1 神经元发出信号，这一结论得到了大约 35%的弓状 kisspeptin 细胞接收 RFRP-3 免疫反应性纤维接触的发现的支持。与前一种情况相反，在两性中，没有 Rfrp 神经元共表达 Kiss1r，而 Tacr3，即神经激肽 B（NKB；一种与弓状 kisspeptin 神经元共表达的神经肽）的受体，在<10%的 Rfrp 神经元中发现。此外，在两性中，kisspeptin 免疫反应性纤维不易与 RFRP-3 细胞毗邻，这进一步排除了 kisspeptin 神经元直接与 RFRP-3 神经元通讯的可能性。最后，尽管 DMN 区域中存在丰富的 NKB，其中 RFRP-3 体位于其中，但在大多数 Rfrp 神经元中并未共表达 NKB。我们的结果表明，在小鼠中，RFRP-3 可能调节一小部分产生 kisspeptin 的神经元，特别是在弓状核中，而 kisspeptin 神经元不太可能对 RFRP-3 神经元有任何直接的相互作用。
