家鸡垂体激素GRP肽生成释放调节机制解析及其在卵巢中的效应探究

It is generally believed that in vertebrates, oocyte growth and maturation is tightly controlled by pituitary gonadotropins (FSH and LH) and local ovarian factors. In our recent study, we found that gastrin-releasing peptide (GRP) is predominantly expressed in the pituitary and its receptor (GRPR) is abundantly expressed in the granulosa cells of early-stage ovarian follicles. This interesting finding led us to hypothesize that in chickens, ‘GRP may act as a novel pituitary hormone and be involved in the control of ovarian follicle development and functions’. To test this hypothesis, using chicken as an animal model, we will investigate that: 1) the specific localization of GRP peptide in the anterior pituitary; 2) the regulation of pituitary GRP peptide synthesis and secretion by hypothalamic factors and ovarian factors (e.g. gonadal steroids; 3) the effects of GRP in the proliferation, differentiation, and apoptosis of ovarian granulosa cells; 4) the roles of GRP on ovarian follicle development and functions. Expectedly, the results from this study will establish a new concept that in chickens, GRP is a novel pituitary hormone and involved in the control of ovarian follicle development at early developmental stages, thus affecting reproduction, such as egg production of chickens.

脊椎动物卵泡发育机制一直是人们关注科学命题。卵母细胞在垂体促性腺激素以及卵巢产生的多种‘旁分泌/自分泌’因子的协同作用下，发育成熟。申请人在最近研究中发现：胃泌素释放肽(gastrin-releasing peptide, GRP)主在家鸡垂体中高表达，且其受体在早期阶段卵泡颗粒细胞中高表达。该结果提示：“GRP或可作为一种新型垂体肽类激素，参与家鸡卵泡发育与卵巢功能调节”。为验证该假说，本项目拟设计体内、体外实验, 解析：1) GRP肽在家鸡垂体中的细胞定位； 2）下丘脑因子与性腺激素对垂体GRP肽生成释放的调节; 3）GRP肽对卵泡颗粒细胞增殖、分化与凋亡的调节；4）GRP肽对卵泡发育与卵巢功能的影响。本研究结果有望首次在家鸡中，建立 “GRP是一种新型垂体激素，可调节卵巢发育与功能”这一新概念。同时，亦为探讨GRP肽对家鸡繁殖性状(如产蛋量)的影响奠定基础。

脊椎动物卵泡发育机制一直是备受人们关注的科学命题。卵母细胞在垂体激素以及其自身产生的多种‘旁分泌和自分泌’因子作用下发育成熟并为受精作好充分准备。为验证“GRP肽是一种新型垂体激素”的假说，本项目设计体内、体外实验, 解析GRP肽在家鸡垂体中的生成释放调节机制同时探究GRP肽在卵巢中的生理效应。本项目研究进展顺利，完成了主要研究目标。主要研究结果包括：1) GRP肽主要定位于垂体促性腺激素细胞中。2）下丘脑因子(GnRH1等)、性激素（雌激素、雄激素孕酮等）参与对家鸡垂体GRP肽生成释放调节。在培养垂体细胞中，GnRH1可高效刺激GRP肽的生成与释放，E2可刺激GRP mRNA的表达；相反，孕酮（P4）和DHT5α可抑制GRP mRNA的表达；3）发现GRP肽依赖其受体GRPR参与家鸡卵泡颗粒细胞增殖。4）GRP 肽可协同垂体激素FSH, LH 参与早期卵泡发育。5）初步探究内源性GRP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GRP肽是一种新型垂体激素参与家鸡卵泡发育，本研究为后续品种选育等提供理论依据。