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Role of VDR and PXR in Steroid and Xenobiotic Regulation Across Species

This study examines the interactions of various ligands with vitamin D receptor (VDR) and pregnane X receptor (PXR) across multiple species, including humans, zebrafish, and Xenopus laevis. We highlight the high-affinity binding of 1,25-(OH)2-vitamin D3 and the low-affinity binding of lithocholic acid, emphasizing their role in upregulating CYP3A expression. The research investigates the developmental roles of zebrafish PXR and the tissue distribution changes due to PXR activation loss, as well as the specificity of different PXR variants across species.

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Role of VDR and PXR in Steroid and Xenobiotic Regulation Across Species

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  1. ? Other ligands Sea lamprey VDR 1,25-(OH)2-vitamin D3 (high affinity) Lithocholic acid (low affinity); ability to upregulate CYP3A expression Human VDR Mouse VDR ? Role in zebrafish development Zebrafish PXR Strong activation by benzoates (developmental role); altered tissue distribution from other PXRs loss of activation by steroids and bile salts BXRa (Xenopus laevis) Single ancestral gene BXRb (Xenopus laevis) Androstane and pregnane steroids, C27 bile alcohol sulfates; ability to upregulate CYP3A expression Chicken PXR High constitutive activity CARs (duplication of pre-mammalian PXR) C24 bile acids; broader specificity for steroids and xenobiotics Rabbit PXR Mouse PXR Rat PXR Broadest ligand specificity Dog, pig, rhesus PXRs Human PXR

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