Regulation of human CYP27A1 by estrogens and androgens in HepG2 and prostate cells.
The regulation of the human CYP27A1 gene by estrogens and androgens was studied in human liver-derived HepG2 and prostate cells. Our results show that the promoter activity, enzymatic activity and mRNA levels of CYP27A1 in HepG2 cells are downregulated by estrogen in presence of ERalpha or ERbeta. Similar effects by estrogen were found in RWPE-1 prostate cells. In contrast, estrogen markedly upregulated the transcriptional activity of CYP27A1 in LNCaP prostate cancer cells. 5alpha-Dihydrotestosterone and androgen receptor upregulated the transcriptional activity of CYP27A1 in HepG2 cells. Progressive deletion experiments indicate that the ERbeta-mediated effects in HepG2 and LNCaP cells are conferred to the same region (-451/+42) whereas ERalpha-mediated effects on this promoter are more complex. The results indicate that the stimulating effect of androgen in HepG2 cells is conferred to a region upstream from -792 in the CYP27A1 promoter. In summary, we have identified the human CYP27A1 gene as a target for estrogens and androgens. The results imply that expression of CYP27A1 may be affected by endogenous sex hormones and pharmacological compounds with estrogenic or androgenic effects.
Tang
Wanjin
W
Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Uppsala, Sweden.
Norlin
Maria
M
Wikvall
Kjell
K
D000728:Androgens / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000378:metabolism; D053493:Cholestanetriol 26-Monooxygenase / Q000096:biosynthesis* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D002762:Cholecalciferol; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase