家鸡新型垂体激素CART肽的生成释放调节机制解析及其在卵巢中的作用初探

Cocaine- and amphetamine-regulated transcript (CART) peptide has been reported to be abundantly expressed in the central nervous system including hypothalamus and play important roles in the regulation of many physiological processes, including food intake and stress. However, our recent studies showed that CART is predominantly expressed in chicken anterior pituitary, and its secretion from pituitary can be induced by elevated intracellular cAMP and calcium levels. Moreover, CART mRNA levels in the pituitary display sexual difference, and the plasma CART levels increase progressively during sex maturation. All the findings led us to hypothesize that: 1) CART peptide is a novel hormone produced by pituitary and, like other classic peptide hormone (e.g. GH and LH), its expression and secretion is tightly controlled by hypothalamic factors (GnRHs) and sexual steroids; 2) pituitary CART peptide may play critical roles in controlling gonadal development and functions. To substantiate this hypothesis, in this study, both in vivo and in vitro experiments will be carried out to decipher the regulatory mechanisms of CART peptide expression and secretion in chicken anterior pituitary. Moreover, the potential roles of CART peptide in ovarian development and functions will also be investigated. The results from this study will not only help to develop a novel concept that in chickens, CART is a novel member of pituitary peptide hormones, and may be involved in the regulation of gonadal development and functions, but also establish a basis to elucidate the potential roles of CART gene in controlling chicken reproduction trait.

CART肽在哺乳动物中枢神经系统（包括下丘脑）中高表达，参与摄食、应激等生理过程调节。 最近，申请人在解析家鸡垂体功能调节机制进程中，发现：CART肽仅高表达于家鸡垂体，其释放可受胞内cAMP和[Ca2+]水平调节；在家鸡性成熟过程中，垂体CART肽的表达具明显性别差异, 且血液中CART水平亦显著提升。据此，申请人推测：在家鸡中，CART肽是新的垂体肽类激素，与垂体其他肽类激素一致（GH、LH等），其生成释放可受下丘脑因子(或性腺激素)调控，进而作用于靶组织，如性腺等。为验证该假说，本项目拟设计体内、体外实验, 解析CART肽在家鸡垂体中的生成释放调节机制; 同时，亦初探CART肽在其潜在靶组织(卵巢)中的效应。本研究有望首次在家鸡中建立“CART肽是新的垂体激素成员，可参与性腺发育与功能调节”这一新概念, 同时，也为探讨CART肽对家鸡繁殖性状的影响奠定基础。

CART肽在哺乳动物中枢神经系统（下丘脑）中高表达，参与摄食、应激等生理过程调节。申请人在项目支持下，设计系列体内、体外实验, 解析CART肽在家鸡垂体中的生成释放调节机制，同时亦尝试探究CART肽在其潜在靶组织(卵巢)中的效应。本项目研究进展顺利，完成了主要研究目标。具体包括：1) 揭示CART肽主要定位于垂体促性腺激素细胞中。2）揭示在家鸡不同发育阶段(生长、性成熟)血液CART水平的动态变化。 3）揭示下丘脑因子(GnRHs、CRHs、TRH等)、性激素（雌激素、雄激素、孕酮等）等对家鸡垂体CART肽生成释放的调节。4）初步探讨CART肽对家鸡垂体激素（如：LH、GH、ACTH等）生成释放的影响。5）初探CART肽对卵泡颗粒细胞/鞘细胞基因表达的调节。6）初步探究内源性CART肽的消除，对家鸡性腺发育与功能（如卵泡发育、产蛋等）的影响。 系列研究结果支持：CART肽可作为一种受下丘脑控制的新型垂体激素，或可通过影响性腺发育与功能，参与家鸡繁殖过程的调节’这一假设。此外，作为重要经济动物以及最主要禽蛋供应者，针对垂体CART肽的功能探究，有望揭示“新型垂体激素CART肽对家鸡繁殖性能的影响”。这些结果亦为后续品种选育等提供理论依据。