Synthesis of 1,25-Dihydroxyvitamin D in the Nephrectomized Pregnant Rat*

Abstract

Pregnant rats were maintained on diets either adequate or deficient in vitamin D. On the 20th day of gestation, animals were either nephrectomized bilaterally or sham operated. Immediately thereafter, 4 groups of nephrectomized or sham-operated pregnant rats received i.v. [26,27-3H]25-hydroxyvitamin D3 ([26,27-3H]25OHD3), while 2 groups received [1,2-3H,4-14C]D3. The animals were sacrificed 10-24 h later. The distribution of the radiolabeled metabolites of vitamin D3 was determined in extracts of maternal plasma, maternal intestinal tract, placentae and fetuses after Sephadex LH-20 column chromatography. Both vitamin D3 and 25OHD3 crossed the placenta and entered the fetus. In anephric animals receiving [26,27-3H]-25OHD3, 24,25-dihydroxyvitamin D and a polar peak eluting in the position of 1,25-dihydroxyvitamin D [1,25(OH)2D] and 25,26-dihydroxyvitamin D were identified in extracts of maternal plasma and intestinal tracts and of placentae and fetuses. The identities of 24,25-dihydroxyvitamin D and 1,25(OH)2D were confirmed by high pressure liquid chromatography. In rats receiving [1,2-3H,4-14C]D3, approximately 50% of the polar metabolite consisted of 1,25(OH)2D. The anephric pregnant rat is able to synthesize 1,25(OH)2D, the fetal portion of the feto-placental unit is the most likely site of production of this hormone, and this metabolite of vitamin D crosses the placenta from the fetus to the mother.