Evidence for Extra-Renal 1 α-Hydroxylation of 25-Hydroxyvitamin D$_{3}$ in Pregnancy

The kidneys are thought to be the only organs capable of 1 α-hydroxylation of vitamin D and its metabolites. We have examined the in vivo conversion of $^{3}$H-(25,26)-25-hydroxyvitamin D$_{3}$ (25 OHD$_{3}$) to $^{3}$H-(25,26)-1 α,25-dihydroxyvitamin D$_{3}$ [1α,25(OH)$_{2}$D$_{3}$] in vitamin D-deficient, pregnant and nonpregnant rats. As expected, nephrectomy of nonpregnant vitamin D-deficient rats prevented the conversion of 25 OHD$_{3}$ to 1α,25(OH)$_{2}$D$_{3}$. In contrast, nephrectomy of pregnant, vitamin D-deficient rats reduced but did not abolish the formation of 1 α,25(OH)$_{2}$D$_{3}$ from its precursor. The identity of the radioactive metabolite formed from $^{3}$H-25OHD$_{3}$ which circulated in nephrectomized, pregnant rats was established as 1α,25(OH)$_{2}$D$_{3}$ by comigration with synthetic 1 α,25(OH)$_{2}$D$_{3}$ on high-pressure liquid chromatography. The simultaneous absence of 1 α,25(OH)$_{2}$D$_{3}$ in the fetal kidneys indicated that the site of 1α-hydroxylation after nephrectomy of the pregnant rat was probably extrarenal in origin. Two sites of 1 α-hydroxylation of 25OHD$_{3}$, one renal and the other extra-renal, either fetoplacental or maternal, may exist in the pregnant, vitamin D-deficient rat.