Expression of cyclooxygenase-2 and prostanoid receptors by human myometrium

Prostanoids play an important role in the regulation of parturition. All re productive tissues, including fetal membranes, decidua, and myometrium, hav e the capacity to synthesize prostanoids, and fetal membranes have been sho wn to express elevated levels of cyclooxy-genase-2 (Cox-a) at the onset of labor. We have now investigated the expression of Cox-2 in human myometrium . Myometrial samples collected from women in labor during lower segment ces arean section expressed 15-fold higher levels of Cox-2 messenger ribonuclei c acid (mRNA) compared to myometrial specimens collected from women not in labor, as detected by Northern blot analysis. Immunohistochemical detection of Cox-2 protein showed cytoplasmic staining in the smooth muscle cells of the myometrium. Cultured myometrial cells expressed low levels of Cox-2 mR NA under baseline conditions, but interleukin-1 beta (IL-1 beta) caused a 1 7-fold induction of expression of the Cox-2 transcript after incubation for 6 h. IL-1 beta also induced expression of biologically active Cox-a protei n, as detected by immunofluorescence, Western blot analysis, and measuring the conversion of arachidonic acid to prostanoids in the presence and absen ce of a Cox-2-selective inhibitor, NS-398. PGE(2) receptor subtype EP2 mRNA was expressed in cultured myometrial smooth muscle cells, whereas transcri pts for EP1, EP3, EP4, FP, and IP were low or below the detection limit as measured by Northern blot analysis. However, IL-1 beta stimulated expressio n of EP4 receptor mRNA. Our data suggest that expression of Cox-2 transcrip t is elevated at the onset of labor in myometrial smooth muscle cells, whic h may depend on induction by cytokines. As, in addition to Cox-a, the expre ssion of prostanoid receptors is regulated, not only the production of pros tanoids, but also responsiveness to them, may be modulated.