The relative importance of the oligosaccharide units in human chorionic gonadotropin (CG) for LH/CG receptor activation in rat Leydig cells and mouse Leydig tumor cells.
The biological properties of deglycosylated human chorionic gonadotropin (DhCG), obtained by hydrogen fluoride treatment (HF-DhCG) of intact hCG or by oligonucleotide-directed mutagenesis (CHO-DhCG), and that of their fully glycosylated counterparts, were tested in terms of cAMP and steroid production in rat Leydig cells and in mouse Leydig tumor cells (MA-10 cells). In both cell types, HF-DhCG and CHO-DhCG possessed comparable biological activities. The maximum for DhCG-induced cAMP production was approximately 12% of that of intact hCG when tested in rat Leydig cells, and only 2% when tested in MA-10 cells. DhCG possessed significant steroidogenic activity in both cell types. In MA-10 cells the maximum for DhCG-induced steroidogenesis was 30-50% of that of intact hCG, while in rat Leydig cells DhCG and hCG induced similar steroidogenic maxima. Based on its ED50, DhCG possessed 10-17% of the steroidogenic potency of intact hCG in rat Leydig cells, while in MA-10 cells DhCG was only 2-fold less potent than hCG. When accurate hormone-receptor binding data are absent, the intrinsic receptor-stimulating activity of a ligand can still be estimated at full receptor occupancy, provided that over the whole dose range the biological response is proportional to receptor stimulation. The present data show that in transfected MA-10(P+29) cells which over-express rat phosphodiesterase, the hormone-induced stimulation of cAMP and steroid production is directly coupled to receptor activation up to maximal occupation of the LH/CG receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000737:chemistry / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006031:Glycosylation; D006858:Hydrofluoric Acid; D007984:Leydig Cell Tumor / Q000378:metabolism*; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D009844:Oligosaccharides / Q000378:metabolism*; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011967:Receptors, Gonadotropin / Q000378:metabolism*; D013268:Stimulation, Chemical
D006063:Chorionic Gonadotropin; D009844:Oligosaccharides; D011967:Receptors, Gonadotropin; D011284:Pregnenolone; D000242:Cyclic AMP; D006858:Hydrofluoric Acid