title: Abnormal sulfate metabolism in vitamin D-deficient rats.
abstract: To explore the possibility that vitamin D status regulates sulfate homeostasis, plasma sulfate levels, renal sulfate excretion, and the expression of the renal Na-SO4 cotransporter were evaluated in vitamin D-deficient (D-D-) rats and in D-D- rats rendered normocalcemic by either vitamin D or calcium/lactose supplementation. D-D- rats had significantly lower plasma sulfate levels than control animals (0.93+/-0.01 and 1.15+/-0.05 mM, respectively, P < 0.05), and fractional sulfate renal excretion was approximately threefold higher comparing D-D- and control rats. A decrease in renal cortical brush border membrane Na-SO4 cotransport activity, associated with a parallel decrease in both renal Na-SO4 cotransport protein and mRNA content (78+/-3 and 73+/-3% decreases, respectively, compared with control values), was also observed in D-D- rats. Vitamin D supplementation resulted in a return to normal of plasma sulfate, fractional sulfate excretion, and both renal Na-SO4 cotransport mRNA and protein. In contrast, renal sulfate excretion and renal Na-SO4 cotransport activity, protein abundance, and mRNA remained decreased in vitamin D-depleted rats fed a diet supplemented with lactose and calcium, despite that these rats were normocalcemic, and had significantly lower levels of parathyroid hormone and 25(OH)- and 1,25(OH)2-vitamin D levels than the vitamin D-supplemented groups. These results demonstrate that vitamin D modulates renal Na-SO4 sulfate cotransport and sulfate homeostasis. The ability of vitamin D status to regulate Na-SO4 cotransport appears to be a direct effect, and is not mediated by the effects of vitamin D on plasma calcium or parathyroid hormone levels. Because sulfate is required for synthesis of essential matrix components, abnormal sulfate metabolism in vitamin D-deficient animals may contribute to producing some of the abnormalities observed in rickets and osteomalacia.
authors.affiliation: Inserm U 426, Faculté Xavier Bichat and Université Paris VII, France.
authors.forename: I
authors.initials: I
authors.lastname: Fernandes
authors.forename: G
authors.initials: G
authors.lastname: Hampson
authors.forename: X
authors.initials: X
authors.lastname: Cahours
authors.forename: P
authors.initials: P
authors.lastname: Morin
authors.forename: C
authors.initials: C
authors.lastname: Coureau
authors.forename: S
authors.initials: S
authors.lastname: Couette
authors.forename: D
authors.initials: D
authors.lastname: Prie
authors.forename: J
authors.initials: J
authors.lastname: Biber
authors.forename: H
authors.initials: H
authors.lastname: Murer
authors.forename: G
authors.initials: G
authors.lastname: Friedlander
authors.forename: C
authors.initials: C
authors.lastname: Silve
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins; D015870:Gene Expression; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism* / Q000652:urine; D027981:Symporters; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters; D012964:Sodium; D002118:Calcium