Hizuka N, Gorden P, Lesniak M A, Van Obberghen E, Carpentier J L, Orci L
J Biol Chem. 1981 May 10;256(9):4591-7.
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.
诸如人生长激素（hGH）之类的多肽激素与细胞表面结合至少引发三种不同的事件：产生生物信号、配体降解以及受调控的受体丢失。形态学研究表明，配体在生理温度下被细胞内化，并在细胞内与溶酶体结合。诸如氯化铵和氯喹等溶酶体促渗剂以浓度、时间和温度依赖的方式抑制细胞相关的125I-hGH的降解，并促进配体与细胞的不可逆结合。当0.45 nM的hGH在37℃与培养的人淋巴细胞孵育时，在完全相同的浓度、时间和温度条件下，受体丢失与125I-hGH的内化同时发生。氯化铵与亚最大浓度的hGH在诱导受体下调方面具有相加作用。这些研究支持这样的概念，即配体降解和受体丢失通过内化过程与初始受体结合相偶联。
