Differential effects of parathyroid hormone on the renal 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 production of young and adult rats.
In young rats, PTH markedly stimulates the renal conversion of 25-hydroxyvitamin D3 (25OHD3) to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active form of vitamin D3. With increasing age, serum 1,25-(OH)2D3 decreases while serum PTH increases. Therefore, the effect of PTH on the renal metabolism of 25OHD3 to 24,25-(OH)2D3 or 1,25-(OH)2D3 was compared in young and adult rats. Rats were housed in the dark and fed a low Ca, vitamin D-deficient diet for 4-6 weeks, and thyroparathyroidectomy was performed. Renal 25OHD3 metabolism was measured in vitro by incubating renal cortical slices with tritiated 25OHD3 and quantifying tritiated metabolites by high pressure liquid chromatography. When young (2 months old) thyroparathyroidectomized (TPTX) rats were repleted with PTH by ip injection, 1,25-(OH)2D3 production increased 61%, and 24,25-(OH)2D3 production decreased to 40%. When adult (13 months old) TPTX rats were repleted with PTH, there was no increase in 1,25-(OH)2D3, but 24,25-(OH)2D3 production decreased to 43%. When PTH was added in vitro by incubating renal slices from young TPTX rats for 4 h, 1,25-(OH)2D3 production increased 68%, and 24,25-(OH)2D3 production decreased to 71%. In slices from adult rats, 24,25-(OH)2D3 production was decreased significantly to 71%, and 1,25-(OH)2D3 production was unaffected by PTH. The PTH-stimulated increase in the cAMP content of renal slices from adult rats was 75% that of slices from young rats. These studies demonstrate that PTH modulates renal 24,25-(OH)2D3 production in the adult. However, PTH does not modulate renal 1,25-(OH)2D3 production in the adult under the same conditions that produce a PTH effect in the young animal.
D015650:24,25-Dihydroxyvitamin D 3; D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging; D000818:Animals; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000096:biosynthesis*; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013965:Thyroidectomy
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D015650:24,25-Dihydroxyvitamin D 3; D000262:Adenylyl Cyclases; D002117:Calcitriol; D002112:Calcifediol