Receptors, acceptors, and the action of polypeptide hormones: illustrative studies with epidermal growth factor (urogastrone).
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.
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
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