Developmental changes in the responsiveness of rat kidney to vitamin D metabolites.
Kidneys from both normal and vitamin D-deficient rats were found to show changes in responsiveness to vitamin D metabolites during postnatal development, correlated with the concentrations of the specific receptor for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the specific binding protein for 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3]. Cytosol preparations from kidneys of vitamin D-deficient rats, in the second week of life, contained specific binding proteins for 24,25-(OH)2D3. From the fourth week of life, specific receptors for 1,25(OH)2D3 were predominant. In the third week after birth, both the receptor for 1,25(OH)2D3 and the 24,25(OH)2D3 binding protein were present. We have used a sensitive parameter for vitamin D action, the stimulation of creatine kinase BB (CKBB) activity, to measure the response of kidneys from vitamin D-deficient or normal rats. In the first days of life of vitamin D-deficient rats, the kidneys did not respond to either vitamin D metabolite; in the second week of life, there was stimulation of renal CKBB only by 24R,25(OH)2D3; beginning in the fourth week of life, only 1,25(OH)2D3 stimulated renal CKBB. However, during the third week of life, CKBB activity was increased by both metabolites. In normal animals, which showed a lower CK activity at all ages, the response was similar to that in vitamin D-deficient animals but the peak was achieved a few days later. The stimulation of CKBB by vitamin D metabolites occurred in all the zones of the kidneys. An increase in renal CKBB by 1,25(OH)2D3 was also detected immunohistochemically. The increase of CKBB activity caused by the two vitamin D metabolites at different stages of development, closely correlated with changes in the presence of the 1,25(OH)2D3 receptor or the 24,25(OH)2D3 binding protein, suggests a specific role for each metabolite during renal development.
D015650:24,25-Dihydroxyvitamin D 3; D000375:Aging; D000818:Animals; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D014018:Tissue Distribution; D014808:Vitamin D Deficiency / Q000378:metabolism*
C031424:24,25-dihydroxycholecalciferol receptor; D004100:Dihydroxycholecalciferols; D007527:Isoenzymes; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D015650:24,25-Dihydroxyvitamin D 3; D003402:Creatine Kinase; D002117:Calcitriol