Department of Marine Biotechnology (N.Z., J.S., Y.Z.), University of Maryland Baltimore County and Institute of Marine and Environmental Technology, Baltimore, Maryland 21202; Faculty of Agriculture, Food and Environment (M.G., B.L.-S.), The Hebrew University, Rehobot, Israel 76100; and Ifremer (A.S.), Unité de Physiologie Fonctionnelle des Organismes Marins, Laboratoire des sciences de l'environnement marin Unité mixte de recherche 6539, Plouzané 29280, France.
Endocrinology. 2014 May;155(5):1874-86. doi: 10.1210/en.2013-1894. Epub 2014 Jan 31.
Kisspeptin regulates reproductive events, including puberty and ovulation, primarily via GnRH neurons. Prolonged treatment of prepubertal striped bass females with kisspeptin (Kiss) 1 or Kiss2 peptides failed to enhance puberty but suggested a gnrh-independent pituitary control pathway. Kiss2 inhibited, but Kiss1 stimulated, FShβ expression and gonadal development, although hypophysiotropic gnrh1 and gnrh receptor expression remained unchanged. In situ hybridization and immunohistochemistry on brains and pituitaries revealed a differential plasticity between the 2 kisspeptin neurons. The differences were most pronounced at the prespawning phase in 2 regions along the path of gnrh1 axons: the nucleus lateralis tuberis (NLT) and the neurohypophysis. Kiss1 neurons appeared in the NLT and innervated the neurohypophysis of prespawning males and females, reaching Lh gonadotropes in the proximal pars distalis. Males, at all reproductive stages, had Kiss2 innervations in the NLT and the neurohypophysis, forming large axonal bundles in the former and intermingling with gnrh1 axons. Unlike in males, only preovulatory females had massive NLT-neurohypophysis staining of kiss2. Kiss2 neurons showed a distinct appearance in the NLT pars ventralis-equivalent region only in spawning zebrafish, indicating that this phenomenon is widespread. These results underscore the NLT as important nuclei for kisspeptin action in 2 facets: 1) kisspeptin-gnrh interaction, both kisspeptins are involved in the regulation of gnrh release, in a stage- and sex-dependent manner, especially at the prespawning phase; and 2) gnrh-independent effect of Kiss peptides on the pituitary, which together with the plastic nature of their neuronal projections to the pituitary implies that a direct gonadotropic regulation is plausible.
Kisspeptin 主要通过 GnRH 神经元调节生殖事件,包括青春期和排卵。延长对青春期前条纹鲈鱼雌性的 kisspeptin (Kiss) 1 或 Kiss2 肽处理未能增强青春期,但提示存在 gnrh 独立的垂体控制途径。Kiss2 抑制,但 Kiss1 刺激 FShβ 表达和性腺发育,尽管垂体促性腺激素 gnrh1 和 gnrh 受体表达保持不变。脑和垂体的原位杂交和免疫组织化学显示出这两种 kisspeptin 神经元之间存在差异可塑性。在 gnrh1 轴突沿线的 2 个区域,这种差异在产卵前阶段最为明显:外侧结节(NLT)和神经垂体。Kiss1 神经元出现在 NLT 中,并支配产卵前雄性和雌性的神经垂体,在远侧部到达 Lh 促性腺激素细胞。在所有生殖阶段,雄性都在 NLT 和神经垂体中具有 Kiss2 神经支配,在前者形成大的轴突束,并与 gnrh1 轴突交织。与雄性不同,只有排卵前的雌性才有大量的 NLT-神经垂体 kiss2 染色。Kiss2 神经元在产卵斑马鱼的 NLT 腹侧部等效区域显示出明显的外观,表明这种现象很普遍。这些结果强调了 NLT 作为 kisspeptin 在 2 个方面发挥作用的重要核:1)kisspeptin-gnrh 相互作用,两种 kisspeptin 都参与 gnrh 释放的调节,以阶段和性别依赖的方式,特别是在产卵前阶段;2)Kiss 肽对垂体的 gnrh 独立作用,加上其神经元投射到垂体的可塑性,意味着直接的促性腺激素调节是合理的。