Comparative Studies on the In Vitro: DISCUSSION(5)
Several reports have indicated that stimulation of the cAMP signaling pathway is an important factor in deci-dualizing stromal cells. The mechanism by which this is accomplished, however, requires further investigation. Our studies suggest that decidualization, as assessed by IGFBP-1 and prolactin induction, requires several intermediate steps associated with the cAMP signaling pathway. The response to cAMP was not immediate; it required 48 h of stimulation.
This implies that after cAMP activation, additional changes occur within the stromal fibroblasts that in turn initiate the transcription of IGFBP-1 and prolactin. Our preliminary studies suggest that this process requires de novo protein synthesis (unpublished results). It has been well documented that stimulation of the cAMP pathway can affect transcription of certain genes. This occurs through proteins, such as cAMP response element (CRE)-binding protein, CRE modulators (CREM), and inducible cAMP early repressor (ICER), that specifically bind to the CRE region of the promoters. It has recently been shown that during the course of decidualization, human endometrial stromal cells express novel isoforms of CREM as well as exhibiting an up-regulation of ICER. Whether these proteins are essential to the decidualization process remains to be elucidated.