Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical fibroblasts.
Prostaglandins (PGs) cause uterine contraction to initiate labor at term. We investigated the effect of progesterone and 17beta-estradiol on the production of PGE2 in rabbit uterine cervical fibroblasts. When the cervical fibroblasts were treated with interleukin-1alpha (IL-1alpha), the level of PGE2 was augmented in a time- and dose-dependent manner. The IL-1alpha-augmented PGE2 level was almost completely suppressed by progesterone and 17beta-estradiol at the physiological concentration (0.01 microM), whereas a slight decrease in the basal level of PGE2 was observed in the cervical fibroblasts treated with both hormones at a pharmacological concentration (1 microM). In addition, the level of PGE2 augmented by IL-1alpha was due to the increase of cyclooxygenase (COX) activity, which was inhibited by progesterone and 17beta-estradiol as well as by indomethacin and a specific COX-2 inhibitor, NS-398, but not by the well-known COX-1 inhibitor, aspirin. Furthermore, progesterone and 17beta-estradiol suppressed the IL-1alpha-augmented COX-2 production but not the constitutive production of COX-1 in rabbit uterine cervical fibroblasts. These results suggest that progesterone and 17beta-estradiol prevent the initiation of labor by inhibiting PGE2 production after the suppression of COX-2 production during pregnancy in the rabbit.
Department of Biochemistry, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan. satotak@toyaku.ac.jp
T
T
Sato
H
H
Michizu
K
K
Hashizume
A
A
Ito
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts; D006728:Hormones / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011817:Rabbits
D006728:Hormones; D007375:Interleukin-1; D007527:Isoenzymes; D011374:Progesterone; D004958:Estradiol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone