Interrelationship between nitric oxide and prostaglandins in bovine granulosa cells

It is well recognized that prostaglandins of the E (PGE) and F (PGF) series play an important role in ovarian physiology; in addition, nitric oxide (NO) has been recently demonstrated to be an important mediator of granulosa cell function. There is now evidence for a biologic relationship between PGs and the NO biosynthetic pathway. The aim of this study was to investigate the relationship between NO and PGE(2) and PGF(2 alpha) in bovine granulosa. cells. Granulosa cells collected from small (< 5mm) and large (> 8mm) follicles were treated with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) or with indomethacin, an inhibitor of PGs synthesis, and PGE(2) and PGF(2 alpha) were quantified; in addition, the effects of PGE(2), PGF(2 alpha), and indomethacin on steroidogenesis and NO production were determined. The highest concentration of SNAP inhibited (P < 0.001) PGE(2) production in cells from both kinds of follicles, while the lowest dose was effective only in cells from small follicles. The highest concentration of SNAP inhibited and stimulated (P < 0.001) PGF(2) production in cells from small and large follicles, respectively. Progesterone. (P(4)) production was stimulated by PGE(2) and inhibited by PGF(2 alpha)(P < 0.001) in cells from both types of follicles. Estradiol 17 beta (E(2)) secretion was inhibited in cells from small and stimulated in those from large follicles by PGE(2) (P < 0.05), while PGF(2 alpha) was stimulatory in cells from both kinds of follicles (P < 0.001). P(4) production by cells from small follicles was inhibited and stimulated by those from large follicles by indomethacin (P < 0.001), which also increased E(2) output in cells from small follicles (P < 0.001). NO production was inhibited by both PGE(2) and PGF(2 alpha) except at the lowest concentration, which was stimulatory (P < 0.001). Indomethacin stimulated (P < 0.001) NO production. Taken together, the present data suggest a cross-talk between NO and PGs biosynthetic pathways, which needs to be further clarified. (C) 2001 Elsevier Science Inc. All rights reserved.