In order to understand cellular mechanisms by which growth hormone (GH) produces its effects in adipocytes, we propose to combine expertise in cellular and molecular mechanisms of hormone action and receptor structure with broad experience in studying metabolic actions of GH. We shall characterize the regulation of glucose transport by GH in vitro to determine whether it exhibits the insulin-like, transitory and refractory properties unique to other actions of GH. The turnover of receptors will be assessed by measuring rates of receptor synthesis and degradation, and GH receptor recycling will be examined with specific inhibitors and trypsinized cells. Down-regulation of receptors will also be investigated as another indicator of dynamic changes in GH receptors which may correspond to changes in metabolic responses to GH. Structural properties of the GH receptor will be examined by cross-linking techniques, by use of monoclonal antibodies to the GH receptor, and by newly developed methods which increase the refinement in the analysis of GH structure. We shall attempt to purify the GH receptor, and to determine whether it is phosphorylated or has protein kinase activity. In this way, we shall evaluate the relationship between the effects of GH and binding of GH to receptors on adipocytes and the effects in metabolic and growth regulation.
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