The overall goal of the proposed research is to understand the molecular events which permit the regulated, coordinate expression of the pituitary glycoprotein hormone genes, lutropin (LH), follitropin (FSH) and thyrotropin (TSH). Besides being important physiologically for reproduction and metabolic regulation, these proteins provide a good model system for analysis of gene expression of subunit proteins. All three proteins contain a common alpha subunit and a different beta subunit. Initially cDNAs will be isolated for FSH-beta; cDNAs are already available for the other subunits. The cloned cDNAs will be used to study the regulation of subunit mRNA levels, gene transcription and gene structure. Particular attention will be focused on the relationship of alpha subunit gene structure and expression to the structure and expression of the beta subunits. In addition, the interaction of steroid and thyroid hormone receptors with the subunit gene sequences will be examined to gain further insight into DNA sequences possibly involved in regulating gene expression. The function of putative regulatory DNA sequences will then be tested by construction of fusion genes which will be transfected into suitable cells. Finally, an effort will be made to identify protein factors which interact with the glycoprotein hormone genes to facilitate their appropriate expression. These studies should provide increased understanding of the molecular machinery responsible for the regulated expression of the genes for subunit proteins.
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