OBJECTIVES: Human corticotrophin-releasing hormone (CRH) plays a pivotal role in the stress response. Its expression is under the control of various steroid hormones, such as estrogens. The transcriptional activity of the estrogen receptor (ER) may be modified by small-ubiquitin related modifier (SUMO1). In the present study, we aim to reveal the role of SUMO1 in the regulation of ER-mediated CRH promoter activation.
METHODS: CHO-K1 cells were transfected with human ER and SUMO1 expressing plasmids together with the CRH promoter reporter gene. CRH mRNA was detected in BE(2)C cells by real time PCR.
RESULTS: We found that estradiol could elevate CRH promoter activity to a much higher level in cells co-transfected with ER and SUMO1 than that with ER alone, and that the enhancement was blocked by the ER inhibitor, ICI182,780. Furthermore, the endogenous CRH mRNA expression was also increased when the BE(2)C cell were transfected with ERalpha and SUMO1 in contrast to the transfection with ERalpha alone.
CONCLUSIONS: Our results indicate that SUMO1 participates in the modulation of ER-mediated CRH mRNA expression which may be important for the regulation of the stress response....