Interrelationship between nitric oxide and prostaglandins in bovine granulosa cells

Abstract

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 2α 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 2α were quantified; in addition, the effects of PGE 2, PGF 2α 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 2α production in cells from small and large follicles, respectively. Progesterone (P 4) production was stimulated by PGE 2 and inhibited by PGF 2α( P < 0.001) in cells from both types of follicles. Estradiol 17β (E 2) secretion was inhibited in cells from small and stimulated in those from large follicles by PGE 2 ( P < 0.05), while PGF 2α 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 2α 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.