Adenosine differentially amplifies luteinizing hormone- over follicle-stimulating hormone-mediated effects in acute cultures of rat granulosa cells.

Adenosine has been shown to acutely amplify LH-dependent events in luteal cells and FSH-dependent events in granulosa cells. In this study, the specificity of purines on mature rat granulosa cell ATP levels in short term culture was assessed, and a comparison of the relative effect of adenosine on amplification of FSH- and LH-stimulated cAMP accumulation was made. Adenosine rapidly and significantly increased ATP levels in granulosa cells. This effect was maximal (approximately 2-fold) within 60 min of culture and occurred in the absence or presence of FSH or LH. The increase in granulosa cell ATP levels by adenosine was dose dependent, with half-maximal and maximum responses of 10 and 30 microM adenosine, respectively. Dipyridamole (10 microM), a purine transport inhibitor, blocked the adenosine-dependent increase in granulosa cell ATP levels. Adenosine and 5'-AMP were equipotent in increasing cell ATP levels; adenine also increased ATP levels, but was significantly less active (approximately 50% of adenosine), whereas hypoxanthine, inosine, and xanthine were inactive. FSH was consistently found to decrease granulosa cell ATP levels by about 30% in the absence or presence of adenosine, whereas LH had no effect on cell levels of ATP. Both FSH and LH significantly stimulated cAMP accumulation in granulosa cells, but the maximal response to FSH was substantially greater than that to LH. Adenosine significantly amplified cAMP accumulation in response to both FSH and LH, but the effect of adenosine on this response to FSH was modest. Amplification by adenosine of cAMP accumulation in response to LH was substantial and about 2- to 3-fold greater than that seen with FSH. These studies show that purines acutely and specifically increase ATP levels in rat granulosa cells. Since adenosine augments LH-dependent cAMP accumulation to a greater extent than FSH-stimulated cAMP production, we suggest that adenosine may favor premature follicular luteinization and, perhaps, function as a mediator of atresia in the developing follicle.