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THYROID HORMONE ACTION IN THYROTROPIC CELLS

促甲状腺细胞中的甲状腺激素作用

基本信息

批准号：
3152816
负责人：
MARVIN C GERSHENGORN
金额：
$ 18.31万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-08-01 至 1990-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3152816
关键词：
arachidonate calcium metabolism homeostasis hormone regulation /control mechanism inositol phosphates membrane permeability organelles phorbols prolactin radioassay thyrotropin thyrotropin releasing hormone tissue /cell culture

项目摘要

The proposed research involves defining the detailed molecular mechanisms by which thyrotropin-releasing hormone (TRH, thyroliberin) stimulates the secretion (release of preformed hormone) of thyrotropin (thyroid-stimulting hormone, TSH) and prolactin (PRL) from the anterior pituitary gland. Two homogeneous populations of pituitary cells are used in these studies so that one may unambiguously assign changes in various aspects of cellular calcium homeostasis to the appropriate cell type. These are a mouse (LAF1/J) thyrotropic pituitary tumor from which cells are derived for short-term studies in culture (TtT cells) and a cloned cell line (GH3 cells) originally derived from a rat mammotropic pituitary tumor. Some comparative studies in which measurement only of TSH and PRL are made will be performed in vitro using cells derived from normal female Sprague-Dawley rats. It has recently been demonstrated that TRH causes a rapid elevation of cytoplasmic free Ca2+ concentration ([Ca2+])i and it has been proposed that this increase in [Ca2+]i serves to couple, at least in part, stimulation by TRH to secretion of TSH and PRL. In this proposal, further studies of the effects of TRH on [Ca2+]i will be made and additive, synergistic and/or antagonistic effects of other regulators of TSH and PRL secretion will be determined. The cellular pools of calcium mobilized by TRH will be determined in intact and detergent-permeabilized cells. A possible second messenger fuction if inositoltrisphosphate in TRH mobilization of cellular calcium and the mechanism of inositoltrisphosphate action will be studied in detergent-permeabilized cells and in isolated cellular organelles. Lastly, studies will be made of secretagogues, such as arachidonic acid and phorbol esters, that appear to act without causing an elevation of [Ca2+]i. The additivity or synergism of stimulation of secretion by arachidonic acid and phorbol esters with secretagogues tht act via elevating [Ca2+]i will be studied as will their effects on cellular calcium homeostasis. It is believed that a more complete understanding of how TRH acts will serve to expand our understanding of the mechanism of action of many cell-surface interacting regulators and allow us to understand better some pathologic conditions that involve abnormalities in cell regulation.

建议的研究包括定义详细的分子机制。促甲状腺激素释放激素(TRH、促甲状腺激素)通过何种途径刺激促甲状腺激素(促甲状腺激素)的分泌(前形成激素的释放) 激素(激素，TSH)和催乳素(PRL)。二在这些研究中使用了同质的垂体细胞群，因此一个人可以毫不含糊地将细胞的各个方面的变化钙平衡到适当的细胞类型。这些是一只老鼠 (LAF1/J)甲状腺垂体瘤，细胞来源于培养(TTT细胞)和克隆细胞系(GH3)的短期研究细胞)最初来自于大鼠的嗜乳性脑垂体瘤。一些人只测量TSH和PRL的比较研究将用取自正常女性的细胞进行体外实验老鼠。最近的研究表明，促肾上腺皮质激素释放激素会导致血压迅速升高。胞质内游离钙浓度([Ca~(2+)])i的变化，并提出了这种[Ca~(2+)]i的增加至少在一定程度上与 TRH对TSH和PRL分泌的刺激作用。在这项提案中，进一步 TRH对[Ca~(2+)]i的影响的研究将被进行和添加，促甲状腺激素和催乳素其他调节剂的协同和/或拮抗作用分泌物将会被确定。细胞内钙离子池的动员 TRH将在完整和洗涤剂渗透的细胞中进行测定。一个肌醇三磷酸在TRH中可能的第二信使功能细胞内钙的动员与三磷酸肌醇的作用机制将在洗涤剂渗透性细胞中和在分离的细胞器。最后，将对分泌物进行研究，如如花生四烯酸和佛波醇酯，它们似乎不会引起 [Ca~(2+)]的升高I.刺激的相加性或协同性花生四烯酸和佛波酯与促分泌剂的分泌通过升高[Ca~(2+)]i来研究它们对细胞的影响钙稳态。人们相信，更全面地了解 TRH的作用机制将有助于扩大我们对许多细胞表面相互作用的调节因子的作用，并允许我们更好地了解一些涉及心脏异常的病理情况细胞调节。