Possible mechanism for preterm labor associated with bacterial infection. II: Enhancement of endotoxin-stimulated phosphoinositide metabolism by sex steroids in human endometrial fibroblasts.
We have previously reported that bacterial endotoxin stimulated membrane phosphoinositide metabolism, which resulted in liberation of arachidonic acid and preterm initiation of parturition. The aim of this study was to explore whether ovarian steroids alter the stimulation of phosphoinositide turnover by endotoxin. The phosphoinositide turnover was evaluated by [32P] phosphate incorporation into phosphatidic acid (PA) and phosphatidylinositol (PI) in human endometrial fibroblasts. When the cells were exposed to endotoxin from Escherichia colli, 32P-labeling of PA and PI was increased in a dose-dependent manner; EC50 was 10 ng/ml. Preincubation with estradiol-17 beta (1 microM) and progesterone (1 microM) for 24 hours, but not for a few hours, enhanced the rate of the endotoxin-stimulated phosphorylation of the lipids in the fibroblasts by decreasing EC50 value of endotoxin to 1 ng/ml. Estradiol or progesterone alone failed to show any effects. These findings demonstrated that the sex steroids may increase the sensitivity of host cells to endotoxin, suggesting the mechanism(s) by which the preterm labor associated with intra-amniotic infection is initiated.
Khan
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AA
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Imai
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A
Tamaya
T
T
D001424:Bacterial Infections / Q000150:complications*; D002478:Cells, Cultured; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D007752:Obstetric Labor, Premature / Q000209:etiology / Q000503:physiopathology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology
D004731:Endotoxins; D012739:Gonadal Steroid Hormones; D010716:Phosphatidylinositols; D011374:Progesterone; D004958:Estradiol