Corticotrophin-releasing hormone (CRH) interacts with inflammatory prostaglandins and interleukins and affects the decidualization of human endometrial stroma

The hypothalamic neuropeptide, corticotrophin-releasing hormone (CRH), whic h is also produced by human endometrium, has been shown to induce its decid ualization in vitro. This process, induced mainly by progesterone, has char acteristics of an aseptic inflammatory reaction, and is modulated by locall y produced pro-inflammatory factors. In humans, prostaglandin E-2 (PGE(2)) enhances while interleukin (IL)-1 inhibits the decidualizing effect of prog esterone. The aim of the present work was to test the hypothesis that CRH m ight affect the decidualization of human endometrium interacting with these factors. Therefore, we studied its effects on the production of pro-inflam matory interleukins IL-1, IL-6 and of PGE(2) from human endometrial stromal cells in primary culture. The results strongly suggest that CRH decidualiz es stromal cells, as judged by the appearance of cytokeratins and the produ ction of prolactin, two established markers of decidualization. In parallel to its effect on decidualization, CRH also decreased the production of PGE (2), while it increased the production of IL-1 and IL-6. Exposure of endome trial stromal cells to IL-6 also caused decidualization. The data presented here suggest that endometrial CRH regulates the production of local modula tors of decidualization, i.e. PGE(2), IL-1 and IL-6. We postulate that, thr ough the regulation of these factors, CRH acts as a local fine-tuner of dec idualization initiated by progesterone.