The long-term objectives of this research are to understand the molecular and metabolic events that are involved in the actions of glucocorticoid hormones on their target cells. This includes the elucidation of the intracellular regulatory mechanisms that operate physiologically to mediate changes in cellular metabolism and genetic expression as a background for understanding of the molecular mechanisms through which endocrine regulation is superimposed. The efforts will largely be directed to an analysis of the mechanisms through which glucocorticoids alter rates of protein biosynthesis at the level of translation. One of the objectives will be a rigorous examination of a hypothesis that some of the late (after 2 hrs of hormone exposure) inhibitory effects of glucocorticoid hormones on transport and synthetic reactions, including protein biosynthesis, are the cells' response to a glucocorticoid-induced inhibition of cellular ATP production, which in turn leads to small, steady-state changes in ratios of adenine nucleotides. Studies on the lethal actions of glucocorticoids are also underway which focus on the appearance of a novel set of proteins that confirm cellular resistance to glucocorticoid-induced cell killing.
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