Media calcium attenuates mitochondrial 1,25(OH)2D production in phosphorus or vitamin D-deprived rats.
Although PTH and hypophosphatemia are the best known stimulators of 25-hydroxyvitamin D-1 alpha-hydroxylase, 1,25(OH)2D3 production in rats and humans can be modulated by circulating calcium, independent of PTH. To test whether calcium modulates this function directly in mitochondria, we examined effects of calcium on 1 alpha-hydroxylase in isolated mitochondrial preparations under basal and stimulated conditions. Rats were fed a low phosphorus (or matched control) diet for 4 or 7 d or a vitamin D-deficient (or matched control) diet for 2, 4, or 7 wk. Renal mitochondria were isolated and assayed for 1 alpha-hydroxylase activity in the presence or absence of added calcium. Calcium did not alter 1 alpha-hydroxylase in rats on control diets. After 4 d of low phosphorus diet, 1 alpha-hydroxylase was increased 2-fold over basal activity; media calcium prevented this stimulatory response. By 7 d the calcium effect was not evident. After 4 wk of vitamin D deprivation, activity was approximately 30-fold greater than controls; calcium reduced this response significantly (15-fold). A significant, but less marked inhibition of activity by calcium was present in rats subjected to 7 wk of vitamin D deprivation. Extramitochondrial calcium can directly modulate 1,25(OH)2D3 production, but this effect appears to be secondary to the primary physiologic regulators of this function. The calcium effect can be overcome after longer term exposure to phosphorus deprivation, but is sustained in the presence of long term vitamin D deprivation.
Carpenter
T O
TO
Department of Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut 06520-8064, USA.
Ellis
B
B
D000818:Animals; D001481:Basal Metabolism; D002117:Calcitriol / Q000096:biosynthesis*; D002118:Calcium / Q000494:pharmacology*; D003470:Culture Media; D003864:Depression, Chemical; D004032:Diet; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010758:Phosphorus / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012430:Ruthenium Red; D014808:Vitamin D Deficiency / Q000378:metabolism*
D003470:Culture Media; D012430:Ruthenium Red; D010758:Phosphorus; D002117:Calcitriol; D002118:Calcium