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Stephen M Downs1 *
Biology Department, Marquette University, Milwaukee, Wisconsin 1
We have examined adenosine (Ado) suppression of FSH-induced germinal vesicle breakdown (GVB) and its relationship to purine de novo synthesis. Cumulus cell-enclosed oocytes (CEO from eCG-primed, immature mice were cultured 17-18 h in medium containing 4 mM hypoxanthine (HX) or 300 M dibutyryl cAMP (dbcAMP) to maintain meiotic arrest, and FSH was added to stimulate meiotic maturation. In the absence of FSH, Ado (1 to 250 M) had no effect in dbcAMP-arrested CEO but dose-dependently suppressed maturation in HX-treated oocytes. FSH-induced maturation was prevented by Ado, although more effectively in dbcAMP-supplemented cultures. Ado affected the magnitude, but not the kinetics pattern, of the response to FSH. Inosine also blocked meiotic induction, but only in the dbcAMP-arrested oocytes. Purine de novo synthesis was nearly doubled in oocyte-cumulus cell complexes by FSH treatment, and this response was completely prevented by Ado. FSH had no effect on HX salvage, although Ado reduced this activity by 98%. Inosine effects on metabolism were intermediate between the control and Ado groups. Experiments with radiolabeled glucose showed that Ado suppressed FSH activation of the pentose phosphate pathway but did not prevent significant activation of glycolysis. Finally, in cultured follicles from primed mice, hCG-induced maturation was blocked by Ado as effectively as by the purine de novo synthesis inhibitor, azaserine. It is concluded that Ado has an inhibitory action on hormone-induced maturation that is due, at least in part, to suppression of glucose metabolism, leading to compromised purine de novo synthesis.
This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.