REGULATION OF TRH RECEPTOR BIOSYNTHESIS

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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.