Receptor‐Mediated Gonadotropin Action in Ovary

The effect of gangliosides and cholera enterotoxin on 125I choriogonadotropin binding, cAMP formation, protein kinase activation and progesterone production have been studied in isolated rat ovarian interstitial cells. A close correlation was observed between the amount of adenosine 3′:5′‐monophosphate (cAMP) produced in the cells and the extent of the activation of protein kinase in response to cholera enterotoxin and choriogonadotropin. Similarly cholera enterotoxin, like choriogonadotropin, stimulated steroidogenesis in a dose‐dependent and time‐dependent manner. Addition of highly purified ganglioside mixtures abolished the stimulatory effect of cholera enterotoxin on cAMP and progesterone responses, while these agents had no effect on choriogonadotropin‐stimulated responses. Similar results were also obtained when different lutropin preparations were tested. Pretreatment of ovarian cells with gangliosides did not show any enhancement in the extent of steroidgenesis stimulated by toxin or trophic hormones compared to that seen with untreated cells. Both gangliosides and cholera enterotoxin failed to block 125I‐labelled choriogonadotropin binding to ovarian cells. Individual gangliosides GD1a, GD1b, GT1 and GM1 [designated according to Svennerholm (1963) J. Neurochem. 10, 613–623] did not modify gonadotropin binding to ovarian cells. Similarly gangliosides isolated from rat ovary, bovine corpus luteum and rat brain also lacked the ability to modify 125I‐labelled choriogonadotropin binding to cells. Analysis of ovarian cells for gangliosides indicated that major ganglioside was GM3 with trace amounts of other gangliosides including GM1 and more complex gangliosides. The results presented in this communication suggest that gonadotropin binding and subsequent cAMP and progesterone production are not influenced directly by gangliosides. In contrast, choleragen‐stimulated cellular events in the ovarian cells were completely inhibited by gangliosides. This suggests that these two agents exert their effects on the responsive system by interacting through separate components on the cell surface.