Transcriptional regulation of 17beta-hydroxysteroid dehydrogenase type 12 by SREBP-1.

17beta-hydroxysteroid dehydrogenase type 12 (17beta-HSD12) has been demonstrated to be involved in enzymatic conversion of weak estrogen, estrone to more potent one, estradiol. However, this enzyme was also reported to be involved in an elongation of very long chain fatty acid (VLCFA). Many genes involved in lipid metabolism are regulated by the transcription factor termed sterol regulatory element-binding proteins (SREBPs). Results of our present study demonstrated that the existence of putative SRE sequence which is recognized as responsive element for SREBPs in 5'-flanking region of 17beta-HSD12 gene. Results of luciferase assay demonstrated that the transcriptional activity of this SRE sequence depends on the activation of SREBP-1 in HepG2 (hepatocellular carcinoma cell line, human) and SK-BR-3 (breast carcinoma cell line, human). 17beta-HSD12 expression was also induced in the HepG2 cells treated with the absence of sterols in which SREBPs were activated. All these results obtained in this study clearly indicate that SREBP-1 represents one of the transcriptional regulators of human 17beta-HSD12.