Increased production and release of prostaglandin-E2 by human granulosa cells from polycystic ovaries

This study was conducted to compare the levels of prostaglandin E2 (PGE2) released by cultured granulosa cells collected from normally-ovulating women (normal cells, NC) and those with polycystic ovaries (polycystic ovary granulosa cells, POGC). Granulosa cells were collected from 7 normal women and 7 anovulatory women with polycystic ovaries. Both groups underwent laparoscopic oocyte retrieval for gamete intra-fallopian transfer. Cell cultures were carried out under basal conditions and in the presence of various substances known to influence PGE2 biosynthesis. Prostaglandin E2 concentrations in the incubation media were taken as a marker of cyclo-oxygenase activity. Unexpectedly, POGC appeared to release greater amounts of PGE2 compared to the NC. There was no difference between the levels of PGE2 produced by the two types of cells during the first 3 hours after cell explants, whereas a difference (P < 0.01) was observed after 24 and 48 hours of incubation. Interleukin-1 beta enhanced PGE2 secretion (P < 0.01) in both POGC and NC, while lipopolysaccharide increased prostaglandin release only by the NC cells. Indomethacin inhibited PGE2 production to a greater extent in POGC (from -70 to -90% with respect to basal release, P < 0.01) than NC (approximately -50%, P < 0.01). Blockade by indomethacin and the weak inhibitory effect of the glucocorticoid, dexamethasone (P < 0.05 only in NC, and only at 24 hours), provided pharmacological evidence that PG production by granulosa cells in vitro might depend primarily on constitutive cyclo-oxygenase activity.