Stimulation by cyclic nucleotides of prostaglandin E production in isolated graafian follicles

Rat Graafian follicles isolated intact responded to 8-Br-cyclic AMP and 8-Br-cyclic GMP with increased prostaglandin E (PGE) production during a 6 h incubation. By contrast, 8-Br-cyclic IMP, 8-Br-5' AMP and 8-Br-5' GMP were inactive in this respect. The effect of 8-Br-cyclic AMP and 8-Br-cyclic GMP was noted only after a lag period of about 4 h. Choleragen, LH, and the phosphodiesterase inhibitor (3-isobutyl-l-methyl-xanthine; IBMX) also stimulated PGE production. Actinomycin D and cycloheximide given simultaneously with 8-Br-cyclic AMP or LH prevented the stimulatory effect of these agents. Concomitant addition of arachidonic acid did not overcome the effect of these inhibitors. Administration of hCG in vivo or incubation with LH in vitro did not elevate endogenous ovarian free arachidonate, while PGE production was enhanced. Dexamethasone prevented this stimulatory effect of hCG. Collectively, the results suggest that stimulation of ovarian PGE production by cyclic nucleotides and LH is dependent on de novo synthesis of one or more components of the PG synthetase system rather than on substrate availability. Cyclic nucleotides may mediate the stimulatory effect of gonadotropins on PGE production.