Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Neurosci Lett. 2012 Nov 30;531(1):40-5. doi: 10.1016/j.neulet.2012.10.010. Epub 2012 Oct 13.
Kisspeptin, a neuropeptide encoded by Kiss1 gene, plays pivotal roles in the regulation of reproductive function. Recently various stressors and stress-induced molecules such as corticotropin-releasing hormone (CRH) and corticosterone have been shown to inhibit Kiss1 expression in rat hypothalamus. To determine whether CRH and glucocorticoids directly act on kisspeptin neurons, we examined the colocalization of CRH receptor (CRH-R) and glucocorticoid receptor (GR) in kisspeptin neurons in the female rat hypothalamus. Double-labeling immunohistochemistry revealed that most kisspeptin neurons in the anteroventral periventricular nucleus and periventricular nucleus continuum (AVPV/PeN), and arcuate nucleus (ARC) expressed CRH-R. We also observed a few close appositions of CRH immunoreactive fibers on some of kisspeptin neurons in AVPV/PeN and ARC. On the other hand, most kisspeptin neurons in AVPV/PeN expressed GR, whereas only a few of kisspeptin neurons in ARC expressed GR. Altogether, our study provides neuroanatomical evidence of the direct modulation of kisspeptin neurons by CRH and glucocorticoids and suggests that stress-induced CRH and glucocorticoids inhibit gonadotropin secretion via the kisspeptin system.
Kisspeptin 是一种由 Kiss1 基因编码的神经肽，在生殖功能的调节中起着关键作用。最近的研究表明，各种应激源和应激诱导分子，如促肾上腺皮质激素释放激素（CRH）和皮质酮，可抑制大鼠下丘脑 Kiss1 的表达。为了确定 CRH 和糖皮质激素是否直接作用于 kisspeptin 神经元，我们检查了雌性大鼠下丘脑 kisspeptin 神经元中 CRH 受体（CRH-R）和糖皮质激素受体（GR）的共定位。双重免疫组织化学显示，前脑室下核和脑室下核连续核（AVPV/PeN）和弓状核（ARC）中的大多数 kisspeptin 神经元表达 CRH-R。我们还观察到在 AVPV/PeN 和 ARC 中的一些 kisspeptin 神经元上有 CRH 免疫反应纤维的一些紧密贴合。另一方面，AVPV/PeN 中的大多数 kisspeptin 神经元表达 GR，而 ARC 中的少数 kisspeptin 神经元表达 GR。总的来说，我们的研究提供了神经解剖学证据，表明 CRH 和糖皮质激素可以直接调节 kisspeptin 神经元，并表明应激诱导的 CRH 和糖皮质激素通过 kisspeptin 系统抑制促性腺激素的分泌。
