Production of C-24- and C-23-oxidized metabolites of 1,25-dihydroxycholecalciferol by cultured kidney cells (LLC PK1) and their presence in kidney in vivo.
1,25-Dihydroxy[3H]cholecalciferol was converted into several more-polar metabolites by a cultured pig kidney cell line (LLC PK1). The production of metabolites was stimulated by pretreating the cells with unlabelled 1,25-dihydroxycholecalciferol. A similar profile of metabolites was observed on high-pressure-liquid-chromatographic analysis of an extract from the kidneys of rats dosed intravenously with 1,25-dihydroxy[3H]cholecalciferol. Among the metabolites detected were 1,24,25-trihydroxycholecalciferol, 1,25-dihydroxy-24-oxocholecalciferol, 1,23,25-trihydroxy-24-oxocholecalciferol and 1,25-dihydroxycholecalciferol-26,23-lactone. The results are in accord with data reported for intestinal 1,25-dihydroxycholecalciferol metabolism [Napoli, Pramanik, Royal, Reinhardt & Horst (1983) J. Biol. Chem. 258, 9100-9107]. These data indicate that C-23- and C-24-oxidation of 1,25-dihydroxycholecalciferol are phenomena common to calciferol target tissues, and that regulation of 1,25-dihydroxycholecalciferol homoeostasis is dependent on the rate of its metabolism in addition to the rate of its synthesis.
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006887:Hydroxycholecalciferols / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D006887:Hydroxycholecalciferols; C013721:1,24,25-trihydroxyvitamin D3; C026947:1,25-dihydroxyvitamin D3-26,23-lactone; C038789:1,23,25-trihydroxyvitamin D3; D002117:Calcitriol