Postnatal changes in plasma 1,25-dihydroxyvitamin D3 in sheep: role of altered clearance

The ontogeny of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production and metabolic clearance rates (PR and MCR, respectively) was determined in chronically catheterized fetal (postconceptional age of 127 days; term = 145 days), neonatal (10 +/- 1 and again at 24 +/- 1 days postnatal), and adult (3 yr of age) sheep. Plasma concentrations of 1,25(OH)2D3 were more than twofold higher in fetuses than in adults and were increased by 78% during the 1st 24 days postnatally. In contrast, compared with values in fetuses, the MCR of 1,25(OH)2D3 was reduced by 40% in 10-day-old neonates and by 58% in 24-day neonates, although 24-day neonatal values were still 75% higher than adult values. In contrast, the PR of 1,25(OH)2D3 did not demonstrate an ontogenic change during development and remained at all times approximately ninefold the adult value. The finding, by regression analysis of an inverse relationship between the MCR and the plasma concentration of 1,25(OH)2D3, is interpreted to suggest that increased plasma concentrations are the result of a reduced MCR. We conclude that increases in plasma concentrations of 1,25(OH)2D3 in the perinatal period can occur by a mechanism that is independent of enhanced endogenous synthesis, namely a reduction in the MCR of the hormone.