STUDIES ON THE MECHANISM OF ACTION OF THE INHIBITORY EFFECT OF PROSTAGLANDIN-F2-ALPHA-ON CYCLIC-AMP ACCUMULATION IN RAT CORPORA-LUTEA OF VARIOUS AGES

In vivo administration of prostaglandin F 2α (PGF 2α) to PMSG treated immature rats drastically reduced the in vitro effect of LH on cAMP accumulation in 7-day-old corpora lutea (CL) but failed to do so in 3-day-old CL. In vitro administration of PGF 2α 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 PGF 2α as low as 0.05 μM significantly inhibited the LH induced rise in cAMP accumulation in 7-day-old CL. A 100 times higher concentration of PGF 2α 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 PGF 2α. A potent phosphodiesterase inhibitor, IBMX, had no effect on the PGF 2α-induced decrease of the LH effect. Furthermore, no change in the phosphodiesterase enzyme activity was observed in the CL after PGF 2α treatment. PGF 2α when tested in combination with PGE 2, did not inhibit the increase in cAMP produced by PGE 2. The results illustrate that the inhibitory effect of PGF 2α on the LH-induced rise in cAMP accumulation is highly dependent upon the age of the CL and that this effect of PGF 2α is not exerted through changes in the phosphodiesterase enzyme activity. These results give further support to the possibility that changes in the cAMP response are one of the earliest steps in PGF 2α-induced luteolysis.