Study of the molecular mechanisms involved in GnIH control of reporduction in chickens

与大多数脊椎动物一样，鸟类的生殖是由下丘脑-垂体-性腺轴控制的，每个组成部分都分泌特定的因子和激素。直到最近，人们认为，这一轴是唯一的刺激控制下，增加一天的长度刺激释放促性腺激素释放激素（GnRH）从下丘脑，其次是促黄体激素和促卵泡激素分泌的垂体腺。然而，最近一种新的抑制性下丘脑肽（促性腺激素抑制激素或GnIH）的发现挑战了这一现有的教条。尽管如此，GnIH作用的确切分子机制仍然未知，拟议的研究旨在阐明其在轴的每个水平的作用。在下丘脑内，我建议确定控制性成熟前后GnIH表达的因素。在垂体水平，我将确定促性腺激素如何整合和反应刺激（通过GnRH）和抑制（通过GnIH）输入。此外，将阐明这种双重控制对垂体功能的影响。在性腺水平上，我建议检查可能的自分泌/旁分泌行动的GnIH睾丸发育和功能。基于我们多年来积累的数据，我开发了一个模型，总结了鸡性成熟前后发生的分子事件。这项研究的结果将有助于验证这一模型，并可以外推到提高家禽养殖的繁殖效率，以及设计新的治疗策略来控制野生和宠物鸟类的繁殖。

As for most vertebrates, reproduction in birds is controlled by the hypothalamo-pituitary-gonadal axis and each component secretes specific factors and hormones. Until recently, it was believed that this axis was exclusively under stimulatory control with an increase in day length stimulating the release of gonadotropin releasing hormone (GnRH) from the hypothalamus, followed by luteinizing hormone and follicle stimulating hormone secretion by the pituitary gland. However, recently the discovery of a novel inhibitory hypothalamic peptide (gonadotropin inhibitory hormone or GnIH) challenged this existing dogma. Nonetheless, the exact molecular mechanisms involved in GnIH action are still unknown and, the proposed research aims at elucidating its effects at every level of the axis. Within the hypothalamus, I propose to determine the factors controlling GnIH expression around sexual maturation. At the pituitary level, I will determine how gonadotropes integrate and react to stimulatory (via GnRH) and inhibitory (via GnIH) inputs. Furthermore, the effect of this dual control on pituitary function will be clarified. At a gonadal level, I propose to examine possible autocrine/paracrine actions of GnIH on testicular development and function. Based on data we accumulated over the years, I have developed a model summarizing molecular events occurring around sexual maturations in chickens. Results from this study will help verify this model, and could be extrapolated to improve reproduction efficiency in poultry farming as well as designing new therapeutic strategies to control reproduction in wild and pet birds.