Adaptation of middle aged rats to long-term restriction of dietary vitamin D and calcium

Abstract

Previous studies have shown that middle aged rats do not increase renal 1,25-dihydroxyvitamin D 3(1,25(OH) 2D 3) production in response to short-term (4 weeks) dietary vitamin D and calcium restriction. The purpose of the experiments reported here was to determine if middle aged rats demonstrate adaptation to long-term restriction of dietary calcium and vitamin D and to compare that adaptation to the adaptation seen in young rats. Middle aged (14–16 months) Fischer 344 rats were fed either a 0.02% calcium, vitamin D-deficient (restricted) or a 1.2% calcium, vitamin D-replete (control) diet. Rats from each group were sacrificed after 1.5, 3.0, 4.5, and 6.0 months on the diets. Renal conversion of 25(OH)D 3 to 1,25(OH) 2D 3 and 24,25(OH) 2D 3 was measured in vitro using isolated renal cortical slices. Renal 1,25(OH) 2D 3 production in the restricted group was not significantly increased until 3 months and reached a maximum of 85% higher than the control at 4.5 months. Renal 24,25(OH) 2D 3 production was significantly decreased after only 1.5 months of restriction and was decreased maximally by 70% at 3.0 months. Serum calcium remained in the range 11–12 mg/100 ml in both diet groups, and serum immunoreactive PTH (iPTH) was modestly increased one- to twofold in the restricted group compared to the control group. In contrast, young rats (3 months old) fed the deficient diet for 1 month had a fourfold increase in renal 1,25(OH) 2D 3 production and a 71% decrease in 24,25(OH) 2D 3 production. Feeding the deficient diet also produced a 43% reduction in serum calcium and a 13-fold increase in serum iPTH. These findings demonstrate that middle aged rats do alter their 25(OH)D metabolism in response to long-term vitamin D and calcium restriction. However, both the rapidity and the magnitude of the response is decreased compared to that seen in the young rat. This blunted vitamin D response in the middle aged rat reflects the lack of a decrease in serum calcium and the marginal increase in serum iPTH in response to vitamin D and calcium restriction.