Corticotropin-releasing hormone (CRH) targets the human myometrium during pregnancy. The efficiency of CRH actions is determined by expression of functional receptors (CRH-R), which are dynamically regulated. Studies in myometrial tissue biopsies using quantitative RT-PCR demonstrated that the onset of labour, term or pre-term, is associated with a significant 2-3 fold increase in CRH-R1 mRNA levels. Detailed analysis of myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding the CRH-R1 variant during labour and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1 as an important regulator of myometrial CRH-R1 gene expression, since prolonged treatment of myometrial cells with IL-1 (1ng/ml) for 18h induced expression of CRH-R1 mRNA levels by 1.5-2 fold whilst significantly attenuating CRH-R1 mRNA expression by 70%. In contrast, IL-1 had no effect on CRH-R1d mRNA expression. Studies employing specific inhibitors suggest that ERK1/2, p38MAPK and downstream nuclear translocation of NF-B mediate IL-1 effects on myometrial CRH-R1 gene. However, the increased CRH-R1 mRNA expression was associated with a dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP signalling cascade. Thus, our findings suggest that IL-1 is an important regulator of CRH-R1 expression and functional activity and this interaction might play a role in the transition of the uterus from quiescence to active contractions necessary for the onset of parturition.