Biosynthesis of Thyrotropin Releasing Hormone

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Thyrotropin releasing hormone (TRH) plays a central role in the hopothalamic-pituitary-thyroid axis. Despite nearly twenty years of work, virtually nothing is known about the regulation of TRH production. Dr. Goodman and collaborators propose to use a recently isolated TRH cDNA and TRH-producing cell line to characterize the factors and mechanisms that underlie TRH biosynthesis. He will use intact animals to compare TRH-like mRNAs in discrete brain regions and a rat cell line to identify agents that affect TRH biosynthesis and secretion. He will also test whether the TRH precursor can generate peptides in addition to TRH that affect pituitary function. Finally, he will use the TRH-producing cell line to identify the components of the TRH gene that are important for regulated and tissue-specific expression. Elucidation of the factors and mechanisms that control TRH biosynthesis and secretion would greatly increase our understanding of how the brain regulates endocrine function.