Response of human amnion cells in culture to 1,25-dihydroxycholecalciferol: Increased 25-hydroxycholecalciferol 24-hydroxylase activity and prostaglandin E₂ formation

We investigated the possibility that 1,25-dihydroxycholecalciferol acts in human amnion as a physiologic calcium ionophore to effect increased prostaglandin E₂ production in this tissue. This possibility was based on the propositions that (1) this metabolite of vitamin D₃ acts in other target tissues, that is, bone, intestine, chorioallantoic membrane, kidney, and intestine, to effect increased calcium absorption, (2) that 1,25-dihydroxycholecalciferol is present in amniotic fluid, which bathes the amnion, and (3) that the mobilization of calcium in amnion is associated with stimulation of enzymes, namely, phospholipase A₂ and phosphatidylinositol-specific phospholipase C that act ultimately to effect the release of arachidonic acid, which in turn leads to increased prostaglandin E₂ production. We found that human amnion cells, maintained in primary monolayer culture, are responsive to 1,25-dihydroxycholecalciferol. Treatment of these cells with 1,25-dihydroxycholecalciferol for 18 hours brought about the induction, in a dose-dependent manner, of 25-hydroxycholecalciferol 24-hydroxylase, a marker of 1,25-dihydroxycholecalciferol action. In addition, treatment of human amnion cells in monolayer culture with 1,25-dihydroxycholecalciferol caused, within 12 hours, a significant increase in the synthesis of prostaglandin E₂, which was maintained for the duration of treatment, that is, 48 hours. These findings may be indicative of a significant physiologic role for 1,25-dihydroxycholecalciferol in metabolic processes that are important in amnion, including transport, amniotic fluid volume homeostasis, and the initiation of parturition.