Studies on the Mechanism of Action of the Inhibitory Effect of Prostaglandin F2α on Cyclic AMP Accumulation in Rat Corpora Lutea of Various Ages1

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Abstract
In vivo administration of prostaglandin F2.alpha. (PGF2.alpha.) to pregnant mare''s serum gonadotropin treated immature rats drastically reduced the in vitro effect of lutropin [LH] on cyclic [c]AMP accumulation in 7 day old corpora lutea (CL) but failed to do so in 3 day old CL. In vitro administration of PFG2.alpha. added simultaneously with LH, reduced the LH effect on cAMP accumulation in 7 and 3 day old CL but not in 1 day old CL. A concentration of PGF2.alpha. as low as 0.05 .mu.M significantly inhibited the LH induced rise in cAMP accumulation in 7 day old CL. A 100 times higher concentration of PGF2.alpha. was needed to reduce the LH effect in 3 day old CL, while 1-day-old CL were completely resistant to the inhibitory effect of PGF2.alpha.. A potent phosphodiesterase inhibitor, isobutylmethylxanthine, had no effect on the PGF2.alpha.-induced decrease of the LH effect. No change in the phosphodiesterase enzyme activity was observed in the CL after PGF2.alpha. treatment. PGF2.alpha., when tested in combination with PGE2, did not inhibit the increase in cAMP produced by PGE2. The inhibitory effect of PGF2.alpha. on the LH-induced rise in cAMP accumulation evidently is highly dependent upon the age of the CL. This effect of PGF2.alpha. is not exerted through changes in the phosphodiesterase enzyme activity. Changes in the cAMP response may be one of the earliest steps in PGF2.alpha.-induced luteolysis.