Prostaglandin F(2alpha) (PGF) induces a rapid reduction in progesterone production (functional luteolysis) followed by tissue degeneration and cell death (structural luteolysis). Reactive oxygen species (ROS) including nitric oxide (NO) play crucial roles in the luteolytic action of PGF. The local concentration of intraluteal ROS is controlled by superoxide dismutase (SOD), the main enzyme involved in the control of intraluteal ROS. To clarify the roles of NO in the regulation of SOD in luteolysis, we examined the effects of NO on SOD expression and activity in cultured bovine luteal endothelial cells (LECs) during short-term (2 h, mimicking functional luteolysis) and long-term (24 h, mimicking structural luteolysis) incubation. We also investigated whether NO modulates PGF production by LECs. LECs were isolated from mid-luteal phase CLs, and exposed to NONOate (a NO donor) for 2 or 24 h. SOD mRNA expression was stimulated by NONOate (10-100 microM) at 2 h (P<0.05). Moreover, 10 microM NONOate stimulated SOD protein expression and SOD activity at 2 h (P<0.05), whereas NONOate inhibited SOD mRNA and protein expressions at 24 h (P<0.05). NONOate stimulated PGF biosynthesis at both incubation times. The overall findings suggest that NO differently regulates SOD in cultured LECs, depending on the exposure time. Acute elevation of SOD may represent a response of LECs to protect themselves against oxidative stress induced by PGF during functional luteolysis, whereas a later reduction of SOD levels by NO may facilitate an excess of intraluteal ROS during structural luteolysis.