INVITRO EFFECTS OF PROGESTERONE AND ESTRADIOL ON UTERINE PROSTAGLANDIN PRODUCTION IN THE PREGNANT RAT

Uterine prostaglandin (PG) levels increase markedly at the end of pregnancy in the rat and steroid hormones appear to be important regulators of this augmentation. The purpose of the present study was to examine the in vitro effects of progesterone (P) and estradiol (E2) on uterine PGE and PGF production in the pregnant rat. Uterine tissue was removed at Days 19 and 21 of pregnancy and incubated with P or E2 (0.1, 1, 10, 100, and 1 000 ng/ml) for 48 h in Ham's F-10 medium at 37-degrees-C. P significantly (p < 0.05) inhibited PGE and PGF production in a dose-dependent manner at Day 19, but not at Day 21 of pregnancy. In contrast, E2 had no effect (p > 0.05) at either day of pregnancy. In a second study, P was found to inhibit uterine PGE production at Days 15 and 19, but not at Day 21 or at delivery. A third study determined that the levels of P were greatly reduced in media containing uterine tissue from delivery when compared to media containing tissue from day 15 of pregnancy (p < 0.05). In a fourth experiment, no difference in tritium-labeled P uptake was detected between media containing uterine tissue from Day 15 of pregnancy and media containing uterine tissue removed at delivery. This observation in association with data from the literature suggests that the disappearance of P from the media in experiment 3 might be due to enhanced P metabolism rather than to differential uptake of P by the tissue. In summary, P is a potent in vitro inhibitor of uterine PG production at Days 15 and 19 of pregnancy, but not at Day 21 or delivery in the pregnant rat. The results suggest that the loss of the inhibitory effect of P on uterine PG production at the end of pregnancy may be partially due to enhanced P metabolism by the uterus. In contrast to P, E2 had no direct in vitro effect on uterine PG production at Days 19 or 21 of pregnancy.