title: Retinoic acid cross-talk with calcitriol activity in Atlantic salmon (Salmo salar).
abstract: Vitamins A (VA) and D (VD) are metabolised by vertebrates to bioactive retinoic acid (RA) and calcitriol (CTR). RA and CTR involvement in bone metabolism requires fine-tuned regulation of their synthesis and breakdown. In mammals antagonism of VA and VD is observed, but the mechanism of interaction is unknown. We investigated VA-VD interactions in Atlantic salmon (Salmo salar L.) following i.p. injection of RA and/or CTR. VA metabolites, CTR, calcium (Ca), magnesium (Mg) and phosphorus (P) were determined in plasma. Expression of bone matrix Gla protein (mgp), collagen 1 alpha2 chain (col1a2) and alkaline phosphatase (alp) mRNA was quantified to reflect osteogenesis. Branchial epithelial Ca channel (ecac listed as trpv6 in ZFIN Database) mRNA levels and intestinal Ca and P influx were determined to study Ca/P handling targets of RA and CTR. RA-injection (with or without CTR) decreased plasma CTR-levels three- to sixfold. CTR injection did not affect RA metabolites, but lowered CTR in plasma 3 and 5 days after injection. Lowered plasma CTR correlated with decreased mgp and col1a2 expression in all groups and with decreased alp in CTR-injected fish. RA-treated salmon had enhanced alp expression, irrespective of reduced plasma CTR. Expression of ecac and unidirectional intestinal influx of Ca were stimulated following RA-CTR treatment. Plasma Ca, Mg and P were not affected by any treatment. The results suggest cross-talk of RA with the VD endocrine system in Atlantic salmon. Enhanced Ca flux and osteogenesis (alp transcription) in RA-treated fish and inhibition of mgp expression revealed unprecedented disturbance of Ca physiology in hypervitaminosis A.
authors.affiliation: National Institute of Nutrition and Seafood Research, PO Box 2029 Nordnes, N-5817 Bergen, Norway. robin.ornsrud@nifes.no
authors.forename: R
authors.initials: R
authors.lastname: Ørnsrud
authors.forename: E J
authors.initials: EJ
authors.lastname: Lock
authors.forename: C N
authors.initials: CN
authors.lastname: Glover
authors.forename: G
authors.initials: G
authors.lastname: Flik
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000821:Animal Feed; D000818:Animals; D017756:Aquaculture; D015415:Biomarkers / Q000097:blood; D002117:Calcitriol / Q000097:blood* / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000493:pharmacokinetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005396:Fish Products; D008274:Magnesium / Q000097:blood; D010758:Phosphorus / Q000097:blood / Q000493:pharmacokinetics; D010938:Plant Oils / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000502:physiology; D000072516:Retinoic Acid 4-Hydroxylase; D020317:Salmo salar / Q000502:physiology*; D000074242:Sunflower Oil; D014212:Tretinoin / Q000097:blood* / Q000494:pharmacology*; D014801:Vitamin A / Q000097:blood; D000097568:Matrix Gla Protein
chemical_list: D000469:Alkaline Phosphatase; D015415:Biomarkers; D002117:Calcitriol; D002118:Calcium; D002135:Calcium-Binding Proteins; D024043:Collagen Type II; D003577:Cytochrome P-450 Enzyme System; D016326:Extracellular Matrix Proteins; D008274:Magnesium; D010758:Phosphorus; D010938:Plant Oils; D000072516:Retinoic Acid 4-Hydroxylase; D000074242:Sunflower Oil; D014212:Tretinoin; D014801:Vitamin A; D000097568:Matrix Gla Protein