REGULATION OF TRH RECEPTOR BIOSYNTHESIS

申请人的培训和研究兴趣与 神经内分泌系统的功能和控制。长期的 这项建议的目的是阐明 神经肽促甲状腺激素释放激素(TRH)在糖尿病控制中的作用 脑下垂体激素分泌和神经生物学。更确切地说， 这项提议的目的是研究分子事件 负责TRH的荷尔蒙和神经活动。至 为了达到这个目的，一种编码受体的互补DNA For TRH将利用非洲爪哇卵母细胞表达系统进行克隆。 蛋白质的序列将被推导出来，并与其他 神经肽受体序列。TRH受体的cDNA将是 将其引入细胞系以确认功能性受体是 由该基因编码，并研究转录和转录后。 受体调控的转录水平。生成的探测 将被用来定位中枢神经系统中的细胞 表达TRH受体mRNA的系统，并将其与 有关TRH的组织结合的信息。同样，这些探测器 将被用于杂交研究，以研究对 内源性TRH受体mRNA在细胞系和原位表达。更好的 对TRH诱导的细胞事件的理解应该提供 关于神经元控制垂体功能的重要信息 以及下丘脑激素的功能多样性。

The applicant's training and research interests relate to the functions and control of the neuroendocrine system. The long-term objective of this proposal is to elucidate the role of the neuropeptide thyrotropin-releasing hormone (TRH) in the control of pituitary hormone secretion and neurobiology. More specifically, the aims of this proposal are to investigate the molecular events responsible for the hormonal and neuronal actions of TRH. To accomplish this aim, a complementary DNA that encodes the receptor for TRH will be cloned, using Xenopus oocyte expression system. The sequence of the protein will be deduced and compared to other neuropeptide receptor sequences. The TRH receptor cDNA will be introduced into cell lines to confirm that functional receptor is encoded by the cDNA and to investigate transcriptional and post- transcriptional levels of receptor regulation. Probes generated with the cDNA will be used to map the cells in the central nervous system which express the TRH receptor mRNA, and compare this to information about tissue binding of TRH. Similarly, these probes will be used in hybridization studies to study the regulation of endogenous TRH receptor mRNA in cell lines and in situ. A better understanding of TRH-induced cellular events should provide important information about neuronal control of pituitary function and the functional diversity of hypothalamic hormones.