Growth hormone (GH) is of major importance in controlling linear growth. A deficiency of the hormone due to lack of proper regulatory stimuli or other causes leads to dwarfism. An excess of the hormone also has deleterious effects and may participate in the pathogenesis of certain diseases. Thus, it is important to understand in detail how GH gene expression is controlled. The gene for growth hormone is also of interest as a model for understanding developmental biology and hormone action because its expression in highly tissue-specific and is regulated by several different classes of factors including thyroid and glucocorticoid hormones. Cultured rat pituitary tumor (GC) cells express the endogenous rat(r) GH gene and are a useful model system to study GH gene expression. Research to date with endogenous rGH gene and transfected intact and mutate rGH and human(h) GH genes and segments of them linked to other genes has demonstrated the presence of sequences on the genes that respond to tissue-specific factors. glucocorticoid and thyroid hormones, and insulin. In the proposed studies it is planned to use GC and other cell types, gene transfer, DNA-protein binding, cell-free transcription and other methods to: define the thyroid hormone control element(s) of the rGH gene and examine its mechanism of action; define the DNA elements of the rGH gene that participate in its tissue-specific expression; identify the insulin-response elements of the rGH and hGH genes: isolate and characterize proteins that bind to the rGH gene; and, examine the cell-free transcription of the rGH gene. These studies will provide a better understanding of the factors that control GH gene expression. The information should be useful for understanding the physiology and pathophysiology of GH in health and disease, and should also provide primary insights into the basic mechanisms of the actions of thyroid and other classes of hormones as well as tissue-specific gene expression.
