title: 20β-hydroxysteroid dehydrogenase gene promoter: potential role for cyclic AMP and xenobiotic responsive elements.
abstract: Teleostean 20β-hydroxysteroid dehydrogenase (20β-HSD) is involved in final oocyte maturation and steroid hormone metabolism. It has structural and functional similarities to mammalian carbonyl reductases that are involved in the metabolism of endogenous carbonyl and xenobiotic compounds. To understand the transcriptional regulation of 20β-HSD, here we report the cloning of 20β-HSD promoter from two fish species, rainbow trout and air-breathing catfish. Analysis of the promoter motifs, in silico identified the presence of several sites for transcription factor binding including cAMP, xenobiotic and steroid hormone responsive elements. Luciferase reporter assays with progressive deletion constructs demonstrated that 20β-HSD type B of trout has no promoter activity while 20β-HSD type A of trout and catfish 20β-HSD promoters showed basal promoter activity. A TATA box flanked by a CAAT box is important for basal transcription. Deletion of cAMP responsive element in the promoter decreased basal promoter activity significantly. Reporter assays with forskolin and IBMX, drugs that increase intracellular cAMP induced the promoter activity over the basal level. Intriguingly, β-nafthoflavone, an arylhydrocarbon receptor ligand, induced the 20β-HSD promoter activity and is further evidenced by the induction of 20β-HSD expression in the livers of catfish, in vivo. These results demonstrate for the first time that 20β-HSD expression is not only modulated by cAMP but also by xenobiotics and further studies may provide significance to the ubiquitous distribution and broad substrate specificity of this enzyme.
authors: Department of Animal Sciences, School of Life Sciences-Centre for Advanced Studies, University of Hyderabad, P.O. Central University, Hyderabad 500 046, Andhra Pradesh, India.
authors: G
authors: G
authors: Sreenivasulu
authors: B
authors: B
authors: Senthilkumaran
authors: C C
authors: CC
authors: Sudhakumari
authors: G
authors: G
authors: Guan
authors: Y
authors: Y
authors: Oba
authors: H
authors: H
authors: Kagawa
authors: Y
authors: Y
authors: Nagahama
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002397:Catfishes / Q000235:genetics* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003349:Cortisone Reductase / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D017686:Oncorhynchus mykiss / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics; D013045:Species Specificity; D015262:Xenobiotics / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology
chemical_list: D010726:Phosphodiesterase Inhibitors; D011994:Recombinant Proteins; D015262:Xenobiotics; D005576:Colforsin; D019324:beta-Naphthoflavone; D004247:DNA; D000242:Cyclic AMP; D003349:Cortisone Reductase; D015056:1-Methyl-3-isobutylxanthine