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

Abstract

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.

Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

“…The observed increase in maternal plasma 1,25(OH) 2 D 3 concentration over the last third of normal pregnancy confirms the findings of previous investigations in the rat (Halloran et al 1979, Verhaeghe et al 1988b, Paulson et al 1990. As the expression of both renal calbindins has previously been shown to be vitamin-Ddependent (Thomasset et al 1982), this increase is likely to stimulate gene expression and may account for the increase in calbindin-D mRNA levels in the kidney that we have demonstrated here.…”

Extrarenal expression of the 25-hydroxyvitamin D-1-hydroxylase

“…In fact, there is no correlation between the maternal and fetal serum levels of 1,25(OH)2D [33] with total concentrations of 1,25(OH)2D on the fetal side of the placenta, from either fetal artery of vein, always lower than that of the mother [34]. The second point to be emphasized is that the increase in maternal 1,25(OH)2D levels during pregnancy is at least partially due to expression of the CYP27B1 and 1-hydroxylating activity in the maternal kidney and not the result of decreased clearance of the hormone from the maternal circulation [35, 36]. With these two realities in mind then, what is the evidence that 1,25(OH)2D produced by the placenta, incompassing both fetal and maternal elements, is a source for 1,25(OH)2D reaching the circulation of the mother?…”

The Role of Vitamin D in Pregnancy and Lactation: Insights from Animal Models and Clinical Studies

“…Studies in pregnant rats, sheep, and rabbits have shown that the higher levels are achieved by increased production of calcitriol and not decreased metabolic clearance (30,110,119). The main source of calcitriol in humans and animals is the maternal kidneys, which upregulate the 1α-hydroxylase two-to fivefold (36,86).…”