Differential actions of gangliosides on gonadotropin and cholera enterotoxin stimulated adenosine3':5' cyclic monophosphate dependent protein kinase in isolated rat ovarian cells.

Received January 16,1978 SUMMARY: Rat ovarian cells were exposed to cholera enterotoxin, and the effect on progesterone synthesis as well as on protein kinase stimulation was examined. Cholera enterotoxin stimulated ovarian steroidogenesis in a dose dependent manner similar to that of hCG. The stimulation of protein kinase by cholera toxin was followed by a lag period, whereas hCG effect was imnediate. Mixed gangliosides, when added to the incubation medium, blocked the cholera enterotoxin-stimulated protein kinase activity and abolished the decrease in exogenous [sH] cyclic AMP receptor activity brought about by the toxin. In contrast, under similar experimental conditions ganglioside addition elicited no effect on protein kinase activation produced by hCG or LH. The data suggest that gangliosides do not appear to be directly involved in gonadotropin binding to ovarian cell membrane and subsequent mediation of physiological response. The available evidence suggests that adenosine 3':5' cyclic monophosphate (cyclic AMP) may be the intracellular mediator of gonadotropin mediated steroidogenesis in ovarian cells (l-6). Previous studies from this laboratory have shown that gonadotropins stimulate protein kinase in rat ovarian cells (4, 5). To evaluate further on the role of protein kinase in gonadotropin stimulated steroidoqenesis, we have investigated the effects of cholera enterotoxin on protein kinase activation in rat ovarian cells. This agent was chosen because cholera enterotoxin has been shown to mimic the action of several peptide hormones in their target tissues (7, 8). Furthermore, the existence of sequence analogies between cholera enterotoxin, LH, hCG, FSH and TSH (9, 10) suggests that all these agents may act through similar mechanisms and possibly through the involvement of qangliosides. Recent studies on ganglioside inhibition of LH and hCG binding to testis plasma membrane further