The initial step in the action of growth hormone (GH) is interaction with specific sites localized in target cell membranes. Growth hormone receptors have been demonstrated in different tissues and have been extensively studied in the liver. 125I-human growth hormone injected IV in the intact male rat is internalized in the hepatocytes by a receptor-mediated process; the radioactive material is sequentially associated with plasma membranes, endocytic structures and lysosomes. A dramatic decrease in the number of hepatic growth hormone receptors has been demonstrated in several situations of growth defect in the rat. GH, insulin and estrogens play a role in the regulation of hepatic growth hormone receptors, but their mechanism of action is not clear. GH receptors have been partially purified; the binding subunit has an approximate MW of 110,000 in rat hepatocytes and adipocytes and in IM-9 lymphocytes, a MV of 50 to 70,000 in rabbit liver. Monoclonal antibodies raised against the GH receptor will facilitate studies of receptor structure and function. The postreceptor events in growth hormone action are unknown. No second messenger or mediator has been demonstrated. Elucidation of the early events that follow activation of the growth hormone receptor is a priority.

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