title: Modified expression of aryl hydrocarbon receptor-related genes by deoxymiroestrol, a phytoestrogen, in mouse hepatocytes in primary culture.
abstract: BACKGROUND
  Deoxymiroestrol (DM), a strong phytoestrogen from Pueraria candollei Wall. ex Benth. var. mirifica (family Leguminosae). This plant has long been used in traditional medicine for rejuvenation.
  
  
  METHODS
  The expression of aryl hydrocarbon receptor-related genes in mouse hepatocytes in primary culture was quantified by real-time RT-PCR and hepatic microsomal P450 activity was assessed by using ethoxyresorufin O-dealkylation.
  
  
  RESULTS
  The mRNA expression of the aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and CYP1A1 was suppressed, whereas that of CYP1B1, estrogen receptor α (ERα), CYP2B9, and glutathione-S-transferase a2 (GSTa2) was increased. The effects of DM on the gene expression depended on treatment period and concentrations, and were similar to those of β-estradiol (E2). DM and E2 at pharmacological concentrations had a marked synergistic effect on CYP1A1 expression after combined treatment with a typical CYP1 inducer, β-naphthoflavone (βNF), at the level of both transcription and enzymatic activity. DM enhanced the inducible mRNA expression of CYP1A1 and CYP1B1 similar to E2. Meanwhile, the expression of ERα mRNA was not affected by βNF, which, on the contrary, completely eliminated the DM-induced mRNA expression of ERα, CYP2B9, and GSTa2.
  
  
  CONCLUSIONS
  The findings that DM modified the expression of several metabolism-related genes suggest the need for caution when using health supplements having phytoestrogenic activity.
authors.affiliation: Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Latiporn
authors.initials: L
authors.lastname: Udomsuk
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Jarukamjorn
authors.forename: Waraporn
authors.initials: W
authors.lastname: Putalun
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakuma
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nemoto
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008519:Medicine, Traditional; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010078:Oxazines / Q000378:metabolism; D048789:Phytoestrogens / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D029908:Pueraria / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000302:isolation & purification / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D003374:Coumarins; D003577:Cytochrome P-450 Enzyme System; D004958:Estradiol; D047628:Estrogen Receptor alpha; D005982:Glutathione Transferase; D007527:Isoenzymes; D010078:Oxazines; D048789:Phytoestrogens; D010936:Plant Extracts; D018336:Receptors, Aryl Hydrocarbon; D013256:Steroids; C484722:Ahr protein, mouse; C497397:Arnt protein, mouse; C406602:deoxymiroestrol; C007649:ethoxyresorufin; C119995:glutathione S-transferase alpha