LIPOPOLYSACCHARIDES INHIBIT PROLACTIN AND RENIN RELEASE FROM HUMAN DECIDUAL CELLS

Human decidual tissue consists of a heterogeneous population of cells, including stromal cells, lymphocytes, and macrophages. Lipopolysaccha rides (LPS), which bind to specific cell surface receptors on macropha ges, have been shown to increase prostaglandin production by the decid ua and amnion. To determine whether LPS may also affect decidual hormo ne production, we have examined the effects of LPS on the synthesis an d release of prolactin and renin. Dispersed cells from term decidual t issue exposed to LPS L2880 (Escherichia coli, 1 mu g/ml) released sign ificantly less prolactin and renin thin control cells after 24 h of ex posure. Maximal inhibition of prolactin (31.6%) and renin (62.5%) rele ase was noted at 72 and 96 h of exposure, respectively (p less than or equal to 0.0002 in each instance). The inhibition of prolactin and re nin release was dose-dependent, with half-maximal inhibition at a dose of approximately 10 ng/ml. LPS caused a decrease in prolactin synthes is as web as release. In addition, LPS inhibited the stimulation of pr olactin release in response to insulin, a known secretogogue of prolac tin release. After 24, 48, and 72 h of exposure, the magnitude of the stimulation of prolactin release by cells exposed to insulin (100 ng/m l) in the presence of LPS (1 mu g/ml) was 84.5, 57.5, and 35.2% less, respectively than that of cells exposed to insulin alone (p = 0.0001 i n each instance). LPS L6011 (Salmonella endotoxin) also inhibited prol actin and renin release. LPS had no effect on overall protein or DNA s ynthesis and did not cause release of alkaline phosphatase and lactate dehydrogenase. Since gram-negative bacteria that cause intrauterine i nfections release LPS, some of the morbidity associated with intrauter ine infections may be due, in part, to inhibition of decidual prolacti n and renin expression. This inhibition may be a direct effect of LPS on the decidual cell or may be mediated by cytokines released by macro phages activated by LPS or by activation of the arachidonic acid pathw ay.