Polycyclic aromatic hydrocarbons modulate the activity of Atlantic cod (Gadus morhua) vitamin D receptor paralogs in vitro

• Atlantic cod has two vitamin D receptors (Vdra and Vdrb) with similar tissue expression. None of the tested PAHs were able to modulate Vdr activation alone. Phenanthrene, fluorene, pyrene antagonized calcitriol-mediated Vdra. Chrysene benzo[a]pyrene potentiated both Vdrs. can potentially pathway in fish. Vitamin receptor (VDR) mediates biological function steroid hormone calcitriol, which is metabolically active version D. Calcitriol important for a wide array physiological functions, including calcium phosphate homeostasis. In contrast mammals, harbor one VDR encoding gene, teleosts possess orthologous vdr genes alpha (Vdra) beta (Vdrb). Genome mining identified vdra vdrb paralogs ( Gadus morhua ) genome, further characterized regarding their phylogeny, tissue-specific expression, transactivational properties induced by calcitriol. addition, selected set polycyclic aromatic hydrocarbons (PAHs), naphthalene, phenanthrene, pyrene, chrysene, (BaP), 7-methylbenzo[a]pyrene, assessed ability transcriptional activity gmVdra gmVdrb vitro . Both activated calcitriol potencies, but produced significantly higher maximal fold activation. Notably, none showed agonistic towards However, binary exposures together or gmVdra, while chrysene BaP receptors. Homology modeling, solvent mapping, docking analyses complemented experimental data, revealed putative secondary binding site addition canonical ligand-binding pocket (LBP). was predicted interact sites, whereas docked primarily LBP. Importantly, our data suggest that paralogous gmVdrs interfere activities, thus signaling contribute adverse effects crude oil PAH on cardiac development bone deformities