title: Receptors, acceptors, and the action of polypeptide hormones: illustrative studies with epidermal growth factor (urogastrone).
abstract: The action of polypeptide hormones is discussed in the context of observations made both with receptors, like the ones for epidermal growth factor (urogastrone) (EGF-URO), insulin, and gonadotropin-releasing hormone (GnRH), and with acceptors, like the ones that participate in the adsorptive pinocytosis of substances like cholesterol (low density lipoprotein acceptor), cobalamin (transcobalamin-II acceptor), and asialoglycoproteins (galactose acceptor). The overall processes that both pharmacologic receptors and acceptors undergo subsequent to ligand binding comprise (a) microclustering; (b) aggregation at both coated ("coated pits") and uncoated plasma membrane regions; (c) internalization, with the formation of endocytic vesicles (endosomes or receptosomes); and (d) either recycling of endosomes (receptosomes) to the plasma membrane or fusion of endosomes (receptosomes) with lysosomes, accompanied by proteolytic degradation of the internalized ligand-receptor complex. The relevance of these processes to hormone action is discussed. Further, illustrative studies with EGF-URO are used to highlight general mechanisms that are thought to participate in the action of a variety of peptide hormones. The microclustering event and the concomitant receptor-regulated membrane phosphorylation reactions are emphasized as key plasma-membrane-localized processes that are very likely involved in the rapid (minutes to tens of minutes) of many peptide hormones. For the delayed actions of hormones (hours to tens of hours; e.g., DNA synthesis), the potential importance of nonlysosomal receptor processing, mediated by SH-requiring proteases that generate intracellular receptor fragments, is pointed out. A scheme for the action of EGF-URO is outlined and a model for peptide hormone action is presented that illustrates how multiple chemical mediators of hormone action may result from the combination of a single hormone with its unique receptor.
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins; D002784:Cholesterol / Q000378:metabolism; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors; D006023:Glycoproteins / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D010873:Pinocytosis; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D011966:Receptors, LHRH; D014805:Vitamin B 12 / Q000378:metabolism
chemical_list: D001212:Asialoglycoproteins; D006023:Glycoproteins; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D002784:Cholesterol; D066246:ErbB Receptors; D011972:Receptor, Insulin; D014805:Vitamin B 12