Cell type specificity and protein kinase C dependency on the stimulation of prostaglandin E₂ and prostaglandin F(2α) production by oxytocin and platelet-activating factor in bovine endometrial cells

The regulation of prostaglandin E₂ and prostaglandin F(2a) in primary cultures of epithelial and stromal cells of bovine endometrium was investigated using two physiological agents, oxytocin and platelet-activating factor, and the protein kinase C activator, 4β-phorbol 12-myristate 13-acetate. At the basal level, epithelial cells produced more prostaglandin F(2a) than did stromal cells (P ≤ 0.0001) and stromal cells produced more prostaglandin E₂ than did epithelial cells (P ≤ 0.0001). In the presence of oxytocin, production of prostaglandin E₂ and F(2a) increased in a dose-dependent manner, only in epithelial cells. Stromal cells did not respond to oxytocin, suggesting that the oxytocin response is cell type specific, acting preferentially on the cell type in which prostaglandin F(2a) is the major prostaglandin produced. Platelet-activating factor increased prostaglandin E₂ and prostaglandin F(2a) production in epithelial cells at 1 and 10 pmol l^-1 (PGE₂,: 10 pmol l^-1, P ≤ 0.01; PGF(2α): 1 pmol l^-1, P ≤ 0.02). Stromal cells also responded to platelet-activating factor, but only at high concentrations (PGE₂,: 0.1 μmol l^-1, P ≤ 0.001; PGF(2α): 0.1 μmol l^-1, P ≤ 0.0001). These results further demonstrate the differences in epithelial and stromal cells; epithelial cells are more sensitive to platelet-activating factor than are stromal cells. Phorbol 12-myristate 13-acetate increased prostaglandin production in a dose-dependent manner in both epithelial and stromal cells, indicating that protein kinase C activation can increase prostaglandin production in these cells. Higher concentrations of phorbol 12-myristate 13-acetate down-modulated protein kinase C activity. The role of protein kinase C in oxytocin- and platelet-activating factor-induced increase in prostaglandin was investigated by down-modulating protein kinase C in epithelial cells and subsequently treating the cells with oxytocin and platelet activating factor. Oxytocin- and platelet-activating factor-induced increases in prostaglandin production were not found in protein kinase C-down-modulated cells, suggesting that protein kinase C activation is necessary for this response.