Renal and hepatic 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in piglets suffering from pseudo vitamin D-deficiency rickets, type I.
The piglets examined suffer from rickets and have symptoms similar to those of classic pseudo vitamin D-deficiency rickets, type I (PVDRI), including plasma concentrations of 1 alpha, 25-dihydroxyvitamin D3 considerably lower than in healthy control piglets. It has been suggested that the rachitic piglets have a defective renal 1 alpha,25-dihydroxyvitamin D3 production. The present study shows that partially purified mitochondrial and microsomal cytochrome P450 from kidney and liver of both rachitic and control animals is able to catalyze 1 alpha-hydroxylation of 25-hydroxyvitamin D3. The renal mitochondrial 1 alpha-hydroxylase activity was higher in the rachitic piglets whereas the renal microsomal 1 alpha-hydroxylase activity was decreased. The immunodetectable levels in kidney of a mitochondrial 1 alpha-hydroxylase (CYP27) and a microsomal 1 alpha-hydroxylase (vitamin D3 25-hydroxylase) were correlated with the 1 alpha-hydroxylase activities. The results suggest that the renal microsomal 1 alpha-hydroxylase is affected by the rachitic condition. It is concluded that the primary genetic defect of systemic 1 alpha,25-dihydroxyvitamin D3 deficiency in the rachitic PVDRI piglets does not reside in a defective function or absence of renal mitochondrial 25-hydroxyvitamin D3 1 alpha-hydroxylase. From this, it may also be concluded that PVDRI in man and pig appear to be two different forms of the disease.
Axén
E
E
Department of Pharmaceutical Biosciences, University of Uppsala, Sweden.
Harmeyer
J
J
Wikvall
K
K
D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D002117:Calcitriol / Q000096:biosynthesis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000302:isolation & purification; D005260:Female; D006900:Hydroxylation; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D012279:Rickets / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000032:analysis; D013552:Swine
D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D002117:Calcitriol; D002112:Calcifediol