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Complete dissociation of gonadotropin receptor binding and signal transduction in mouse Leydig tumour cells. Obligatory role of glycosylation in hormone action.
Authors:M R Sairam
Institution:Reproduction Research Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Abstract:Utilizing a clonal cell line of mouse testicular Leydig cells (MA-10 cells) the complete steroidogenic and other hormonal properties of chemically deglycosylated ovine lutropin (DG-LH) and human choriogonadotropin (DG-hCG) were evaluated. In these cells, with the LH receptor-steroidogenic mechanism tightly coupled and in which there are few, if any, spare receptors, both DG-LH and DG-hCG failed to elicit progesterone production, unlike fully glycosylated native LH and hCG. The receptor-binding activity of DG-LH and DG-hCG was 2-3 times that of LH and hCG in competition experiments with radiolabelled hormones. The typical phenomenon of rounding of MA-10 cells induced by LH and hCG was absent when cells were incubated with DG-LH or DG-hCG. This could be directly attributable to their failure to produce cyclic AMP as second messenger. DG-LH and DG-hCG inhibited cell shape changes and steroidogenesis caused by LH and hCG. The deglycosylated hormones were potent antagonists of the action of glycosylated hormones. Delaying DG-hCG (antagonist) addition for up to 1 h after initiation of hCG action was also very effective in preventing further activation of steroidogenesis. Similar effects were produced by addition of affinity-purified anti-hCG antibodies. In affinity cross-linking experiments, both hCG and DG-hCG bound to the same 90 kDa receptor. Studies with MA-10 cells thus provide unequivocal evidence that the presence of antennary sugars in LH and hCG (and perhaps in other similar hormones such as follicle-stimulating hormone and thyroid-stimulating hormone), is essential for signal transduction. Differences observed in the literature in other cellular systems may be attributed to differences in hormone-receptor-effector coupling.
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