Estrogen-induced alterations in cyclic nucleotide and prostaglandin levels in target tissue.

Monitoring uterine cyclic GMP levels in the rat revealed that there was a statistically significant rise at proestrus from the values that are found at other stages of the cycle (estrus, metestrus, diestrus). Concurrent with the increase in cyclic GMP at proestrus was a decrease in cyclic AMP levels. Treatment of ovariectomized rats with estradiol benzoate (1 μg daily for 4 days) caused an increase in uterine cycle GMP levels from 0.04 to 0.10 pmol/mg tissue. Co-administration of progesterone (4 mg/day for 4 days) blocked this estrogen response.Studies of prostaglandin levels in the cycling rat revealed a rise in PGF occurred at proestrus. That the alteration in PGF levels is estrogen related was evident by the fact that treatment of ovariectomized rats with estradiol benzoate (1 μg daily for 4 days) caused a large increase in PGF levels. This action of estrogen upon prostaglandin levels was blocked by co-administration of progesterone (4 mg/day for 4 days). There is clearly a temporal interrelationship between the action of estrogen to increase cyclic GMP and PGF levels. The ability of the prostaglandin synthetase inhibitor, indomethacin, to block the estrogen-induced increase in PGF, with no inhibitory action upon cyclic GMP formation, requires the formation of these two substances to be independent of each other, or the increment in PGF to follow that of cyclic GMP.