Rudolph L M, Bentley G E, Calandra R S, Paredes A H, Tesone M, Wu T J, Micevych P E
Department of Neurobiology, Laboratory of Neuroendocrinology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Integrative Biology, and Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA.
J Neuroendocrinol. 2016 Jul;28(7). doi: 10.1111/jne.12405.
Reproduction involves the integration of hormonal signals acting across multiple systems to generate a synchronised physiological output. A critical component of reproduction is the luteinising hormone (LH) surge, which is mediated by oestradiol (E2 ) and neuroprogesterone interacting to stimulate kisspeptin release in the rostral periventricular nucleus of the third ventricle in rats. Recent evidence indicates the involvement of both classical and membrane E2 and progesterone signalling in this pathway. A metabolite of gonadotrophin-releasing hormone (GnRH), GnRH-(1-5), has been shown to stimulate GnRH expression and secretion, and has a role in the regulation of lordosis. Additionally, gonadotrophin release-inhibitory hormone (GnIH) projects to and influences the activity of GnRH neurones in birds. Stress-induced changes in GnIH have been shown to alter breeding behaviour in birds, demonstrating another mechanism for the molecular control of reproduction. Peripherally, paracrine and autocrine actions within the gonad have been suggested as therapeutic targets for infertility in both males and females. Dysfunction of testicular prostaglandin synthesis is a possible cause of idiopathic male infertility. Indeed, local production of melatonin and corticotrophin-releasing hormone could influence spermatogenesis via immune pathways in the gonad. In females, vascular endothelial growth factor A has been implicated in an angiogenic process that mediates development of the corpus luteum and thus fertility via the Notch signalling pathway. Age-induced decreases in fertility involve ovarian kisspeptin and its regulation of ovarian sympathetic innervation. Finally, morphological changes in the arcuate nucleus of the hypothalamus influence female sexual receptivity in rats. The processes mediating these morphological changes have been shown to involve the rapid effects of E2 controlling synaptogenesis in this hypothalamic nucleus. In summary, this review highlights new research in these areas, focusing on recent findings concerning the molecular mechanisms involved in the central and peripheral hormonal control of reproduction.
生殖过程涉及多种系统中激素信号的整合，以产生同步的生理输出。生殖的一个关键组成部分是促黄体生成素（LH）峰，它由雌二醇（E2）和神经孕酮相互作用介导，刺激大鼠第三脑室室周核吻侧的促性腺激素释放激素（Kisspeptin）释放。最近的证据表明，经典和膜性E2以及孕酮信号通路均参与此途径。促性腺激素释放激素（GnRH）的一种代谢产物GnRH-(1-5)已被证明可刺激GnRH的表达和分泌，并在脊柱前凸的调节中起作用。此外，促性腺激素释放抑制激素（GnIH）投射到鸟类的GnRH神经元并影响其活性。应激引起的GnIH变化已被证明会改变鸟类的繁殖行为，这展示了另一种生殖分子控制机制。在周围组织中，性腺内的旁分泌和自分泌作用被认为是治疗男性和女性不孕症的靶点。睾丸前列腺素合成功能障碍可能是特发性男性不育的原因之一。事实上，褪黑素和促肾上腺皮质激素释放激素的局部产生可能通过性腺中的免疫途径影响精子发生。在女性中，血管内皮生长因子A参与了一种血管生成过程，该过程通过Notch信号通路介导黄体的发育，从而影响生育能力。年龄引起的生育能力下降涉及卵巢促性腺激素释放激素及其对卵巢交感神经支配的调节。最后，下丘脑弓状核的形态变化会影响大鼠的雌性性接受能力。介导这些形态变化的过程已被证明涉及E2对该下丘脑核突触形成的快速影响。总之，本综述重点介绍了这些领域的新研究，关注有关生殖中枢和外周激素控制分子机制的最新发现。
