Polypeptide hormone degradation and receptor regulation are coupled to ligand internalization. A direct biochemical and morphologic demonstration

• Published in: The Journal of biological chemistry 1981-05, Vol.256 (9), p.4591-4597
• Main Authors: Hizuka, N, Gorden, P, Lesniak, M A, Van Obberghen, E, Carpentier, J L, Orci, L
• Format: Article
• Language: English
• Subjects: Ammonium Chloride - pharmacology; Cell Line; Cell Membrane - metabolism; Growth Hormone - metabolism; Humans; Kinetics; Ligands; Lymphocytes; Receptors, Cell Surface - drug effects; Receptors, Cell Surface - metabolism; Receptors, Somatotropin
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)69476-7

Binding of a polypeptide hormone such as human growth hormone (hGH) to the cell surface initiates at least three diverse events: generation of a biologic signal, ligand degradation, and regulated receptor loss. Morphologic studies demonstrate that the ligand is internalized by the cell at physiologic temperature and associates intracellularly with lysosomes. Lysosomotropic agents such as NH4Cl and chloroquine inhibit the degradation of cell-associated 125I-hGH and promote irreversible binding of the ligand to the cell in a concentration, time, and temperature fashion. When 0.45 nM hGH is incubated with the cultured human lymphocyte at 37 degrees C, receptor loss occurs in parallel with the internalization of 125I-hGH under the exact same conditions of concentration, time, and temperature. NH4Cl is additive with submaximal concentrations of hGH in inducing receptor down regulation. These studies support the concept that ligand degradation and receptor loss are coupled to initial receptor binding by the internalization process.