Synthesis of 1,25-Dihydroxyvitamin D₃by Human Placenta in Vitro*

Serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is increased during pregnancy in the human. Until recently the kidney was postulated to be the sole source of this compound. An extrarenal source of 1,25-(OH)2D3 synthesis has been postulated to exist during pregnancy, including its possible production by placenta or decidua. The recent finding that rat placental homogenates could synthesize 1,25-(OH)2D3 from 25-hydroxyvitamin D3 (25-OH-D3) supported this hypothesis; however, whether human placental tissue was also capable of the 1-ahydroxylation of 25-OH-D3 has not been verified. In the present study, physiologically relevant quantities of 1,25-(OH)2D3 were synthesized from 25-OH-D3 in vitro by homogenates of villous tissue obtained from, term human placentas. Net 1,25-(OH)2D3 synthesis was 12.3 ± 7.4 ng/g wet placental tissue (mean ± SD) during a 1-hr incubation period. Washed placental tissue contained no detectable endogenous 1,25-(OH)2D3 (<3 pg/g). The 1,25-(OH)2D3 was tentatively identified by its elution pattern during liquid chromatography in Sephadex-LH 20, during high pressure liquid chromatography on μ-Poracil, and by its reaction in the chick cytosol binding assay for vitamin D metabolites. Net synthesis of 1,25-(OH)2D3 was not found in human decidua and chorion under identical assay conditions. The in vitro synthesis of 1,25-(OH)2D3 by human placenta, derived nearly entirely of fetal tissue, supports the hypothesis that the placenta is at least one source of the increased 1,25-(OH)2D3 found in maternal serum during pregnancy.