Somatostatin、Cortistatin及其多个受体(SSTR)在家鸡垂体中的作用机理初步研究

It has been reported that somatostatin (SS) and its structurally related cortistatin (CST) peptide play important roles in controlling the release of pituitary hormones including growth hormone (GH) in mammals; however, the roles of SS and CST, and their receptors in the pituitary of chickens remains largely unknown. The identification of authentic growth hormone-releasing hormone (GHRH) and its receptors in chickens leads us to hypothesize that SS, CST and their receptors (SSTR) may also play roles in controlling pituitary growth hormone and prolactin secretion, such as inhibition of GHRH-induced GH release. To substantiate this hypothesis, using multiple experimental techniques, present study aims to: 1) determine whether the 5 somatostatin receptors (SSTR) identified in chickens can function as the receptors specific for SS, or CST or for both peptides; 2) investigate the spatio-temporal expression patterns of 5 SSTRs in developing chicken pituitary; 3) to determine whether SS and CST can act as the inhibitory (or stimulatory) factors to regulate the basal levels of pituitary hormone (GH and PRL) expression and secretion, or GHRH (VIP and other factors)-induced hormone (GH and PRL) release. The results from present study will not only establish a basis to elucidate the role of SS and CST in controlling pituitary functions of chickens, but also provide invaluable insights into the conserved roles of SS and CST in the pituitary across vertebrates.

生长抑素(Somatostatin, SS)及其结构相似多肽Cortistatin (CST)在抑制哺乳动物垂体激素(如生长激素)释放过程中起重要作用。但SS和CST对家鸡垂体激素的作用及其调节机制仍待阐明。 本研究拟在申请者成功鉴定家鸡'真正生长激素释放激素(GHRH)'的基础上，围绕SS、CST及其五个受体(SSTR1-5)，采用多种实验方法，探究其对家鸡垂体生长激素和催乳素生成释放的调节机制。内容包括：1) SS和CST可否以5个SSTR作为功能性受体? 2) 5种SSTR在家鸡垂体中的细胞定位；3) SS、CST可否作为抑制（或刺激）因子，参与调节GHRH、VIP等诱导的垂体生长激素和催乳素生成释放，或影响其本底水平？ 研究结果预期在垂体水平上初步构建'SS、CST对家鸡生长激素和催乳素的调控理论模型'。同时，结果亦有望从比较内分泌角度，解析不同脊椎动物类群垂体功能调节机制异同。

垂体是家鸡等脊椎动物的重要内分泌器官，能产生多种激素，包括生长激素(GH)、催乳素(PRL)、促甲状腺素(TSH)、促肾上腺皮质激素(ACTH)等，掌控动物生长、繁殖、代谢、应激等众多生理过程。垂体激素的生成释放受下丘脑因子正、负调控。尽管下丘脑来源的生长抑素(SST)及其结构相似多肽 Cortistatin (CST)在抑制哺乳动物垂体激素释放过程中起重要作用，但关于SST、CST肽对家鸡垂体功能的调节机制仍待阐明。本研究系统探究SST、CST等多肽对家鸡垂体激素，包括生长激素(GH)、催乳素(PRL)、促甲状腺素(TSH)、以及促肾上腺皮质激素(ACTH)生成释放的调节。 结果显示：1) 家鸡SST-14， SST-28，及CST-14多肽具5个功能性受体：SSTR1, SSTR2, SSTR3, SSTR4, SSTR5。 其中， SSTR1-4为SST-14, SST-28 和CST-14的共同受体，而SSTR5是SST-28的特异性受体； 2) SST-14, SST-28, CST-14均可抑制垂体生长激素(GH)的本底释放。同时，也抑制GHRH刺激的生长激素释放；3) SST-28可抑制肠活性多肽(VIP)所刺激的催乳素释放，该效应由SSTR5特异性介导；4) 催乳素在垂体和部分非垂体组织中均有表达，它通过激活各组织中表达的催乳素受体，参与家鸡性状调节; 5) 发现垂体TSH的生成释放受GCGL多肽的专一性调节，但SST、CST对GCGL刺激效应的负向调节机制不明确；6) 发现瘦素(LEP)及其受体在垂体中高表达，表明LEP可作为‘旁分泌或自分泌因子’，参与垂体功能调节；但SST、CST可否调节其表达待阐明；7) 发现NPW可通过激活一个与SSTR同源的NPBWR2, 抑制垂体生长激素、催乳素释放，揭示NPW是又一新型下丘脑抑制因子。本研究初步构建了下丘脑SST、CST以及其他调节因子(GHRH, GCGL，NPW等)对家鸡多个垂体激素的正、负调控模型。这些结果不仅为揭示SST，CST及相关肽对家鸡生长、繁殖、代谢、应激、脂肪沉积等性状的影响奠定理论基础。同时，也为探究其在脊椎动物垂体中的功能提供线索。