Deglycosylated human chorionic gonadotropin. An antagonist to desensitization and down-regulation of the gonadotropin receptor-adenylate cyclase system.
Human chorionic gonadotropin (hCG) was deglycosylated with anhydrous HF and compared with native hCG for binding and biological activity. The deglycosylated hormone (DG-hCG) had the same affinity as hCG for gonadotropin receptors in murine Leydig tumor cells (MLTC-1) but was less than 1% as potent as hCG in stimulating cyclic AMP production in these cells. Exposure of MLTC-1 cells for 30 min to hCG caused a desensitization of hCG-stimulated adenylate cyclase activity, whereas DG-hCG did not induce desensitization even after 4 h. hCG induced down-regulation of hCG receptors; by 4 h, 40% of the receptors had disappeared, whereas there was no receptor loss in cells exposed to DG-hCG for the same time. By 6 h, receptor down-regulation began to occur in the DG-hCG-treated cells and could be mimicked by exposing the cells to dibutyryl cyclic AMP or cholera toxin. Thus, the small increase in cyclic AMP generated by DG-hCG appears to result in some loss of receptors. Cells were incubated with iodinated hCG or DG-hCG for 30 min, washed, and incubated in fresh medium. Both bound ligands were degraded as measured by disappearance of cell-associated radioactivity and appearance of trichloroacetic acid-soluble label in the medium. The half-lives were  3 and 6 h for hCG and DG-hCG, respectively. Our results indicate that DG-hCG in contrast to hCG does not cause either rapid desensitization of hCG-stimulated adenylated cyclase or rapid down-regulation of hCG receptors. Therefore, receptor occupancy alone is insufficient to induce these phenomena.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000378:metabolism*; D006027:Glycosides; D006858:Hydrofluoric Acid; D006868:Hydrolysis; D007700:Kinetics; D007984:Leydig Cell Tumor; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011974:Receptors, LH
D006063:Chorionic Gonadotropin; D006027:Glycosides; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D000262:Adenylyl Cyclases; D006858:Hydrofluoric Acid