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Factors controlling prostaglandin production by guinea-pig endometrial cells
1Department of Pharmacology, University of Edinburgh Medical School, UK.
Abstract:
The main cell type in the guinea-pig endometrium responsible for prostaglandin (PG) F2 alpha production and some of the intracellular mechanisms responsible for PGF 2 alpha synthesis in this cell type have been investigated. The glandular epithelial cells and not the stromal cells were found to be the main prostaglandin forming cells in the endometrium. A23187 (a calcium ionophore), phospholipase A2 and melittin (an activator of endogenous phospholipase A2) increased PGF 2 alpha output from the glandular epithelial cells, although only the action of melittin was specific to this cell type. Phospholipase A2 also increased the intracellular free calcium concentration in both cell types by an action largely dependent upon the presence of extracellular calcium. Protein synthesis inhibitors (actinomycin D, cycloheximide and puromycin), oestradiol, progesterone and aristolochic acid (an inhibitor of phospholipase A2) reduced PGF 2 alpha output from the glandular epithelial cells, although only the inhibitory action of aristolochic acid was specific. Protein synthesis inhibitors also reduced PGF 2 alpha output from stromal cells, and the outputs of PGE2 and 6 keto-PGF 1 alpha from both cell types. The steroid hormones also reduced PGE2 output from stromal cells. The findings indicate that PGF 2 alpha production by the glandular epithelial cells is dependent upon fresh protein synthesis and the activity of endogenous phospholipase A (which is a calcium-requiring enzyme).