Regulation of renal vitamin D hydroxylase activity in vitamin D deficient rats.
The regulation of renal mitochondrial 1-hydroxylase activity in chronic vitamin D deficiency was studied in male rats. These rats were born of mothers who had been raised from weaning (21 days) on a vitamin D deficient diet and who had no detectable serum 1,25-dihydroxycholecalciferol (1,25-(OH)2D) at the time their offspring were weaned (28 days). In the pups, renal mitochondrial 1-hydroxylase activity was undetectable before the 3rd week of life even though the animals were severely hypocalcemic from birth. The 1-hydroxylase activity first became detectable at 26 days of age, rapidly reached a maximum at day 34, then decreased to become undetectable again by 65 days. Throughout this time serum calcium concentration was less than 5.0 mg/dL and serum parathyroid hormone (PTH) concentration, measured by a midmolecule radioimmunoassay, was two- to five-fold greater than that found in vitamin D replete rats. 1-Hydroxylase activity could be restored in the +65-day-old animals by administration of a single dose of 2.5 micrograms vitamin D3. Enzyme activity was detected within 24 h, was maximal at 72 h, and returned to undetectable levels by 96 h after administration of the vitamin. Serum 1,25-(OH)2D which was undetectable before administration of the vitamin D3, was 108 and 458 pg/mL at 16 and 40 h, respectively, after the injection. The serum concentration of this metabolite then decreased progressively to 80 pg/mL by 6 days. 24-Hydroxylase activity first became detectable 48 h after vitamin D administration, increased to a maximum at 96 h, and thereafter decreased to become undetectable by 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D000818:Animals; D002117:Calcitriol / Q000097:blood / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002417:Cattle; D002762:Cholecalciferol / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000652:urine; D004790:Enzyme Induction; D005260:Female; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000652:urine; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000097:blood / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000201:enzymology / Q000378:metabolism*
D010281:Parathyroid Hormone; D010710:Phosphates; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002762:Cholecalciferol; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002118:Calcium