中文摘要
垂体促性腺激素(包括FSH和LH)是调控家畜生殖活动和繁殖力的关键性激素。已有的研究结果证明,促性腺激素周期性和动态性的合成与分泌除受下丘脑和性腺激素的调节外,亦受到转录因子和表观遗传修饰的综合调控,但对其细胞内机制和相关的分子机理仍远未阐明。本项目针对家畜繁殖领域这一关键性科学问题,以该领域内的最新进展和申请者前期的研究结果为基础,系统研究:(1)FSH和LH合成与分泌调控因子(如下丘脑和性腺激素)在垂体细胞内信号转导过程中的作用关系和分子交汇点;(2)下丘脑和性腺激素等通过垂体细胞内的转录因子影响FSH和LH转录调控的分子机理;(3)证明FSH和LH合成与分泌的周期性和稳态性变化是否受表观遗传修饰或/和miRNAs的调控与介导。通过这些内容的研究,从分子水平认识促性腺激素周期性和动态性的合成与分泌的网络调控机制,为猪以及其他家畜的生殖调控和繁殖力的提高提供理论基础和实践指导。
英文摘要
Gonadotropins, including FSH and LH, are the key factors to regulate the livestock reproductive activities and fertility. It has been documented that the synthesis and secretion of the gonadotropins with cyclical and dynamic property is regulated by hypothalamic hormones and sex hormones, and also by transcription factors in gonadotropes and epigenetic modification, but the underlying molecular and cellular mechanisms are still not clear. Focusing on this critical scientific issue in domestic animal reproductionl and basing on the recent progress in the field and previous findings by the applicant, this project is designed to investigate: (1) relations and molecular junctions of regulatory factors in FSH and LH synthesis and secretion (as the hypothalamus and gonadal hormones) in the pituitary cell signal transduction ; (2) molecular mechanism of transcriptional regulation of FSH and LH by hypothalamus and gonadal hormones through transcription factors; (3) to demonstrate whether and how the periodic and homeostatic changes of FSH and LH synthesis and secretion are affected by epigenetic modification and / or regulation and mediation of miRNAs. The results will be critical for our understanding the regulatory mechanisms of gonadotropins synthesis and secretion from the molecular level, and provide the theoretical basis and practical guidance for reproductive regulation and fertility improvement in pigs and other livestocks.
