Hormonal regulation of PGE₂and COX-2 production in rabbit uterine cervical fibroblasts

Abstract

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.

Estrogen suppresses IL-1β-mediated induction of COX-2 pathway in rat cerebral blood vessels

“…This observation has also been reported in microglia (52) and uterine fibroblasts (42). Whether COX-2 and PGE 2 are essential to the expression in the cerebral endothelium of cell adhesion molecules and whether this process is regulated by 17␤-estradiol remains to be elucidated.…”

An Antiprogesterone, Onapristone, Enhances the Gene Expression of Promatrix Metalloproteinase 3/Prostromelysin-1 in the Uterine Cervix of Pregnant Rabbit.

“…In addition, PGE 2 production in the reproductive tract was also down-regulated by progesterone; we recently reported that in rabbit uterine cervical cells, progesterone inhibits the PGE 2 production via the inhibition of COX-2, but not COX-1 production. 34) Very similar regulation by steroid hormones of prostaglandin G/H synthase-2 has been observed in bovine myometrium. 35) In contrast, there have been few reports that describe the effects of antiprogesterone on connective-tissue metabolism; mifepristone suppresses the production of metalloproteinase inhibitors in cultured human and rat granulosa cells.…”

Estrogen Potentiates the Combined Effects of Transforming Growth Factor-β and Tumor Necrosis Factor-α on Adult Human Osteoblast-like Cell Prostaglandin E2 Biosynthesis

“…The steady-state level of COX-1 mRNA was unaffected by the administration of estrogen as well. In these findings, the hOB cells are distinguished from various cell models of human and animal origin that exhibited increased expression of COX-1 or COX-2 following estrogen exposure [47,48,49].The site of estrogen modulation of hOB cell PGE 2 biosynthesis was not determined by the present studies. The observation that PGE 2 production was elevated in estrogen-pretreated samples stimulated by TGFβ and TNF is firmly established, as is the observation that 17β-E 2 treatment did not limit hOB cell PGE 2 biosynthesis.…”

“…The steady-state level of COX-1 mRNA was unaffected by the administration of estrogen as well. In these findings, the hOB cells are distinguished from various cell models of human and animal origin that exhibited increased expression of COX-1 or COX-2 following estrogen exposure [47,48,49].…”