Intensity of lactation modulates renal 1α-hydroxylase and serum 1,25(OH)2D in rats

Renal 25-hydroxyvitamin D-1α-hydroxylase (1α-hydroxylase) activity and serum 1,25-dihydroxyvitamin D [1,25(OH)2D] concentration were measured in lactating rats suckling litters of 3, 6, or 12 pups to determine the effect of increasing lactational intensity on the biosynthesis of 1,25(OH)2D. Serum Ca2+, total Ca, P(i), and immunoreactive parathyroid hormone were also determined. The average daily litter weight gain for each litter size was calculated from the gain over the last 4-6 days of each of three experiments and was used as an index of lactational intensity. Highly significant correlation coefficients were found between 1α-hydroxylase and average daily litter weight gain (r(s) = 0.63, n = 53, P < 0.001), serum 1,25(OH)2D and average daily litter weight gain (r(s) = 0.62, n = 50, P < 0.001), 1α- hydroxylase and serum total Ca (r(s) = -0.52, n = 53, P < 0.001), and average daily litter weight gain and total Ca (r(s) = -0.52, n = 53, P < 0.001). Neither serum phosphorus nor immunoreactive parathyroid hormone correlated significantly with 1α-hydroxylase. In addition, construction of regression models using a stepwise forward variable selection procedure revealed serum total Ca concentration to be a significant predictor for both serum 1,25(OH)2D and renal 1α-hydroxylase in lactating rats. These data support the hypothesis that increasing lactational intensity leads to decreasing serum Ca concentration, resulting in stimulation of 1α-hydroxylase activity and a rise in the serum 1,25(OH)2D level. Because our observations were obtained in intact rats over a narrow range of Ca2+ (1.23-1.45 mM), our data represent the first indication that hypocalcemia in the presence of PTH stimulates 1,25(OH)2D synthesis under physiological conditions.

Duke Scholars

Author Bruce Lobaugh Pathology