FACTORS CONTROLLING PROSTAGLANDIN PRODUCTION BY GUINEA-PIG ENDOMETRIAL CELLS

The main cell type in the guinea-pig endometrium responsible for prost aglandin (PG) F-2 alpha production and some of the intracellular mecha nisms responsible for PGF(2 alpha) synthesis in this cell type have be en investigated. The glandular epithelial cells and not the stromal ce lls were found to be the main prostaglandin forming cells in the endom etrium. A23187 (a calcium ionophore), phospholipase A(2) and melittin (an activator of endogenous phospholipase A(2)) increased PGF(2 alpha) output from the glandular epithelial cells, although only the action of melittin was specific to this cell type. Phospholipase A(2) also in creased the intracellular free calcium concentration in both cell type s by an action largely dependent upon the presence of extracellular ca lcium. Protein synthesis inhibitors (actinomycin D, cycloheximide and puromycin), oestradiol, progesterone and aristolochic acid (an inhibit or of phospholipase A(2)) reduced PGF(2 alpha) output from the glandul ar epithelial cells, although only the inhibitory action of aristoloch ic acid was specific. Protein synthesis inhibitors also reduced PGF(2 alpha) output from stromal cells, and the outputs of PGE(2) and 6-keto -PGF(1 alpha) from both cell types. The steroid hormones also reduced PGE(2) output from stromal cells. The findings indicate that PGF(2 alp ha) production by the glandular epithelial cells is dependent upon fre sh protein synthesis and the activity of endogenous phospholipase A(2) (which is a calcium-requiring enzyme).