Discrepancy between the effects of desialylation of human chorionic gonadotrophin on in vitro ovarian biological activity and on receptor binding.
An in vitro bioassay based on progesterone production by enzymatically-dispersed immature rat ovary cells, was used to investigate the effect of sialidase treatment on the biological activity of human chorionic gonadotrophin (hCG). The potency in this bioassay system and in an ovarian receptor assay were compared, to substantiate possible discrepancies between the effect of this treatment on biological activity and on receptor binding. Ovarian cells responded dose-dependently to the addition of hCG as well as sialidase treated hCG (asialo-hCG). Dose-response curves of hCG and asialo-hCG were parallel and the maximal stimulation levels reached were the same. Sub-maximal doses of hCG and asialo-hCG were additive. The potency of asialo-hCG was 65% of the original preparation. Addition of low concentrations of phosphodiesterase inhibitor resulted in a greatly enhanced sensitivity of the bioassay, but had no effect on the potencies of asialo-hCG and hCG. In contrast to intact gonadotrophins, the receptor assay potency of asialo-hCG was more than three times the bioassay potency. In agreement with this, it was found that when equal amounts of 125I-labelled hCG and asialo-hCG were specifically bound to the ovarian cells, the latter stimulated progesterone production less effectively. It is concluded that there is a discrepancy between the effect of desialylation on the biological activity and on the receptor-binding ability of hCG.
D000818:Animals; D001212:Asialoglycoproteins; D001681:Biological Assay; D006063:Chorionic Gonadotropin / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D009439:Neuraminidase / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*
D001212:Asialoglycoproteins; D006063:Chorionic Gonadotropin; D010726:Phosphodiesterase Inhibitors; D011956:Receptors, Cell Surface; C019263:asialo-human chorionic gonadotropin; D011374:Progesterone; D009439:Neuraminidase