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Identification of the hypothalamic hormone that regulates proliferatin of lactorophs

调节乳酸菌增殖的下丘脑激素的鉴定

基本信息

批准号：
08670081
负责人：
ARITA Jun
金额：
$ 1.22万
依托单位：
Yamanashi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The serum-free culture system of anterior pituitary cells were validated for determining proliferation in vitro of alctortrphs. Estradiol at 10nM increased BrdU-labeling indices of lactotrophs in the presence of a low insulin concentration, but conversely decreased those of lactotrophs in the presence of a high insulin concentration. Dopamine was effective in decreasing BrdU-labeling indices regardless of its concentrations.Thyrotropin releasing hormone (TRH) at 10^<-6> M decreased BrdU-labeling indices of lactotrophs in the absence of bovine serum albumin (BSA). However, TRH ranging 10^<-11>-10^<-9> M was found to increase BrdU-labeling indices in the presence of BSA in serum-free medium. None of vasoactive intestinal peptide, oxytocin, or luteinizing hormone releasing hormone altered BrdU-labeling indices at the concentrations examined.Involvement of cyclic AMP,a second messenger molecule that is considered to mediate the mitogenic actions of the hypothalamic hormones, in the regulation of lactotroph proliferation and its interactions with other signal transduction pathways of extracellular signals were examined. The cyclic AMP-increasing agents forskolin and dibutyryl cyclic AMP (db-cyclic AMP) increased BrdU-labeling indices of lactotrophs in a dose-dependent manner. The stimulatory action of forkolin on lactotroph proliferation was attenuated by PD98059, a inhibitor of mitogen-activated protein kinase (MAPK) kinase, suggesting an interaction between cyclic AMP and signaling pathway for mitogenic growth factors. Furthermore, the result that pretreatment with the dopaminergic agonist bromocriptine blocked the stimulatory action of forskolin but not that of db-cyclic AMP supported the view that dopamine acts on lactortrophs to inhibit the synthesis of cyclic AMP leading to inhibition of proliferation.

对垂体前叶细胞无血清培养系统进行了体外增殖测定。在低胰岛素浓度下，雌二醇在10nM处增加了乳养动物的brdu标记指数，而在高胰岛素浓度下，雌二醇则反过来降低了乳养动物的brdu标记指数。多巴胺无论浓度如何，都能有效降低brdu标记指数。在牛血清白蛋白（BSA）缺乏的情况下，10^<-6> M促甲状腺激素释放激素（TRH）降低了乳养动物的brdu标记指数。然而，在无血清培养基中，在BSA存在的情况下，TRH范围为10^<-11>-10^<-9 >m时，brdu标记指数升高。血管活性肠肽、催产素或促黄体生成素释放激素在检测浓度下均未改变brdu标记指数。环AMP是一种第二信使分子，被认为介导下丘脑激素的有丝分裂作用，参与乳营养细胞增殖的调节及其与细胞外信号的其他信号转导途径的相互作用。环AMP增加剂福斯可林和二丁基环AMP （db-cyclic AMP）呈剂量依赖性增加乳养菌brdu标记指数。有丝分裂原活化蛋白激酶（MAPK）激酶抑制剂PD98059可减弱福克林对乳营养细胞增殖的刺激作用，提示环AMP与有丝分裂生长因子信号通路相互作用。此外，多巴胺能激动剂溴隐亭预处理阻断了福斯克林的刺激作用，而不阻断db-环AMP的刺激作用，这一结果支持了多巴胺作用于乳养细胞抑制环AMP合成从而抑制增殖的观点。