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Regulation of human hepatic estrogen sulfotransferase (SULT1E1) expression by xenobiotics and lipid intermediates.
Author(s) -
Duanmu Zhengbo,
Kocarek Thomas A.,
RungeMorris Melissa A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1184-b
Subject(s) - pregnane x receptor , aryl hydrocarbon receptor , constitutive androstane receptor , lipid metabolism , medicine , chemistry , nuclear receptor , endocrinology , estrogen receptor , sulfotransferase , estrogen , aryl hydrocarbon receptor nuclear translocator , xenobiotic , receptor , liver x receptor , biology , biochemistry , transcription factor , enzyme , gene , cancer , breast cancer
Estrogens regulate hepatobiliary lipid metabolism, and estrogen sulfotransferase (SULT1E1) plays a key role as an estrogen‐inactivating enzyme in the liver and other estrogen target tissues. In this study, the effects of pharmacological activation of xenobiotic‐ or lipid‐sensing pathways on SULT1E1 expression were investigated in primary cultured human hepatocytes by TaqMan RT‐PCR. Treatment with the pregnane X receptor (PXR) ligand, rifampicin (5x10 −5 M), suppressed SULT1E1 mRNA content by ~90% relative to control. Treatment with either of the aryl hydrocarbon receptor (AhR) ligands, β‐naphthoflavone (10 −5 M) or 2,3,7,8‐TCDD (10 −8 M), suppressed SULT1E1 transcript levels by ~70%, while the non‐AhR binding 1,3,7,8‐TCDD analog had no effect on SULT1E1 mRNA content. The activation of lipid‐sensing nuclear receptors, such as the peroxisome proliferator activated receptor α by ciprofibrate (10 −4 M) and the liver X receptor by 24,25(S)‐epoxycholesterol (3x10 −5 M), increased SULT1E1 mRNA content ~3‐fold relative to control. These results suggest that human hepatic SULT1E1 expression is repressed by xenobiotic activators of the PXR and AhR, but induced by metabolic intermediates of lipid metabolism. Supported by ES05823 (M.R.M.), HL50710 (T.A.K.) and ES06636.