Inhibition of the degradation of receptor-bound human choriogonadotropin by lysosomotropic agents, protease inhibitors, and metabolic inhibitors.
A previous report from this laboratory showed that binding of iodine-labeled human choriogonadotropin to Leydig tumor cells is not a reversible process (Ascoli, M., and Puett, D. (1978) J. Biol. Chem. 253, 4892--4899). Most of the cell-bound hormone was found to be degraded to 3'-monoiodotyrosine before being released from the cells, and the degradation process could be inhibited by the lysosomotropic agents NH4Cl, chloroquine, and Triton WR-1339. It is reported herein that the degradation of receptor-bound human choriogonadotropin is an energy-dependent process, which can be inhibited by compounds that interfere with glycolysis or oxidative phosphorylation (e.g. NaF, NaN3, NaCN, and 2-deoxyglucose). Hormone degradation is also inhibited by some protease inhibitors such as the chloromethyl ketones of lysine and phenylalanine, but not by specific trypsin inhibitors (e.g. p-aminobenzamidine and p-tosyl-L-arginine methyl ester). With the exception of NH4Cl, it was found that the compounds which inhibit hormone degradation also inhibit hormone-stimulated steroidogenesis. However, the present results involving dose dependency, and those given in the following paper (Ascoli, M. (1978) J. Biol. Chem. 253, 7839--7843), indicate that these two phenomena are not related.
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D007984:Leydig Cell Tumor / Q000378:metabolism; D008297:Male; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis; D014361:Trypsin Inhibitors / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D011480:Protease Inhibitors; D011956:Receptors, Cell Surface; D013256:Steroids; D014361:Trypsin Inhibitors; D000643:Ammonium Chloride; D002738:Chloroquine