Expression and control mechanisms of prostaglandin H2 synthase in endometrium and decidua

为了明确两种环氧合酶（COX）在蜕膜间质细胞体外培养系统中是否参与PG的产生，我们进行了后续的研究。特异性抗体免疫细胞化学研究显示，6 ~ 8周治疗性流产时获得的蜕膜间质细胞中存在COX-2和COX-1。与COX-1明显组成表达不同，COX-2在培养基中不含血清的情况下通过添加白细胞介素-1 （IL-1）诱导表达。COX-2的基础染色水平明显低于COX-1。黄体酮中加入地塞米松后，无论是酶染色还是PGE2生成，COX-2的诱导作用都减弱，提示黄体酮可能参与了早孕蜕膜抑制前列腺素合成的机制。此外，COX-2的特异性抑制剂NS-398在剂量为10^<-6>M时，剂量依赖性地抑制IL-1刺激的蜕细胞产生PGE2，并完全阻断PG的产生。这些结果表明，在这种体外培养条件下，妊娠早期个体间质细胞产生PG完全依赖于COX-2途径，COX-1活性可能受到不同机制的控制，如花生四烯酸可用性或先前报道的酶抑制蛋白。

In order to clarify the involvement of two types of cyclooxygenase (COX) in decidual PG production, subsequent study was undertaken by using in vitro decidual stromal cells culture system.Immunocytochemical study with specific antibody revealed the presence of COX-2 as well as COX-1 in decidual stromal cells obtained at the time of therapeutic abortion between 6 to 8 weeks. In contrast to COX-1 which was apparently expressed constitutively, COX-2 was induced by the addition of interleukin-1 (IL-1) in the absence of serum in culture medium. The basal staining level of COX-2 was significantly lower than that of COX-1. The addition of dexamethasone of progesterone attenuated the induction of COX-2 in terms of both enzyme staining and PGE2 production, which implied the possible involvement of progesterone in the inhibitory mechanism of prostaglandin synthesis by decidua in early pregnancy. In addition, a specific inhibitor of COX-2, NS-398, dose dependently inhibited the PGE2 production by decidual cells stimulated with IL-1 and completely blocked PG production at the dose of 10^<-6>M.These results suggest that PG production by dedidual stromal cells from early pregnancy wholely depend upon COX-2 pathway in this in vitro culture condition and it seems likely that COX-1 activity may be under control of different mechanism such as arachidonic acid availability or previously reported enzyme inhibitory protein.