Effects of Environmental Chemicals on Bone Metabolism through Steroid and Xenobiotic Receptor (SXR)

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Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chemicals. SXR is highly expressed in the liver and intestine, where it regulates CYP3A4, which in turn controls xenobiotic and endogenous hormone metabolism including active vitamin D. However, it is unclear whether drug additives exert such activity. We found that four of eight drug additives increased SXR-mediated transcription. In particular, acetyl tributyl citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated SXR. Our in vitro and in vivo results suggest that ATBC specifically induces CYP3A in the intestine by activating SXR. We suggest that ATBC-containing products be used cautiously because they may alter metabolism of vitamin D.