Pregnancy does not alter the metabolic clearance of 1,25-dihydroxyvitamin D in rats

Increased circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy could be due to an increase in production or decrease in the metabolic clearance rate of 1,25(OH)2D. To answer this question an isotope dilution method was used to determine the clearance rate of 1,25(OH)2D in pregnant and aged-matched nonpregnant female rats. A bolus of 0.146 muCi 1,25(OH)2[3H]D3 was given to 60 pregnant and 60 aged-matched nonpregnant rats and the disappearance of the isotope was followed in these animals over the next 48 h. In 12 pregnant rats vs. 14 nonpregnant controls not injected with tracer, plasma calcium (9.6 +/- 0.41 vs. 10.7 +/- 0.17 mg/ml) and 25(OH)D (17.1 +/- 1.15 vs. 25.4 +/- 1.58 ng/ml) levels were significantly lower (P less than 0.01 and P less than 0.001), whereas plasma 1,25(OH)2D levels (110 +/- 16.1 pg/ml vs. 77 +/- 6.0 pg/ml) were significantly higher (P less than 0.05). Clearance rates of 1,25(OH)2D of 25.8 +/- 1.31 microliters/min in pregnant rats and 20.2 20.2 +/- 1.38 microliters/min in nonpregnant aged-matched rats were not significantly different. Similarly, the apparent volume of distribution of 1,25(OH)2D in the pregnant rats (15 +/- 1.0 ml) was not significantly different from that in the nonpregnant control animals (18 +/- 2.1 ml). Production rates of.1,25(OH)2D were elevated in the pregnant rats (2.83 pg/min) compared with the nonpregnant controls (1.55 pg/min). In conclusion, the elevated maternal plasma 1,25(OH)2D level during pregnancy is a result of increased production and is not due to a decreased clearance.