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 this metabolite of vitamin D3 acts in other target tissues, that is, bone, intestine, chorioallantoic membrane, kidney, and intestine, to effect increased calcium absorption, that 1,25-dihydroxycholecalciferol is present in amniotic fluid, which bathes the amnion, and 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.
Casey
M L
ML
Griffin
J E
JE
Korte
K
K
Mitchell
M D
MD
MacDonald
P C
PC
D000650:Amnion / Q000166:cytology / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System; D015232:Dinoprostone; D004790:Enzyme Induction; D006706:Homeostasis; D006801:Humans; D011458:Prostaglandins E / Q000096:biosynthesis*; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D065668:Vitamin D3 24-Hydroxylase
D011458:Prostaglandins E; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium