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

对于大多数脊椎动物来说，鸟类的繁殖是由下丘脑-垂体-性腺轴控制的，每个组成部分都会分泌特定的因子和激素。直到最近，人们一直认为这一轴是唯一受刺激控制的，随着日长的增加，刺激促性腺激素释放激素(GnRH)从下丘脑释放，随后黄体生成素和卵泡刺激素由脑下垂体分泌。然而，最近一种新的下丘脑抑制性多肽(促性腺激素抑制激素或GnIH)的发现挑战了这一现有教义。尽管如此，GnIH作用的确切分子机制仍不清楚，拟议的研究旨在阐明其在轴的各个水平上的作用。在下丘脑，我建议确定在性成熟前后控制GnIH表达的因素。在脑垂体水平，我将确定促性腺激素如何整合并对刺激性(通过GnRH)和抑制性(通过GnIH)输入做出反应。此外，这种双重控制对垂体功能的影响将被阐明。在性腺水平，我建议研究GnIH对睾丸发育和功能的可能的自分泌/旁分泌作用。基于我们多年来积累的数据，我开发了一个模型，总结了发生在鸡性成熟周围的分子事件。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鸟类和宠物鸟的繁殖。

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.