Corpus luteum regression is related to an increased generation of
reactive oxygen species. Although several studies indicate that
PGF(2alpha) is involved in regression of the corpus luteum in mammalian species through an increase in
reactive oxygen species, the exact mechanism remains unknown. In the present study, the relationship between
nitric oxide and
PGF(2alpha) in regulation of lipid peroxidation was studied. Ovarian tissue from pseudopregnant rats at mid- (day 5) or late phase or at the time of regression (day 9 of pseudopregnancy) of corpus luteum development was used.
Thiobarbituric acid reactants, used as a lipid peroxidation index, were higher on day 9 of pseudopregnancy than on day 5. In contrast,
glutathione content (an
antioxidant metabolite) was lower on day 9 than on day 5 of pseudopregnancy. These results indicate that there was an enhanced oxidative status in ovarian tissue during luteolysis. Administration of
N(omega)-nitro-L-arginine methyl ester (
L-NAME: 600 micromol l(-1)), a competitive
nitric oxide synthase (NOS) inhibitor, led to a decrease in basal
thiobarbituric acid reactant content in ovarian tissue from rats on day 9 of pseudopregnancy only, indicating that during regression of the corpus luteum, NO could act as intermediary in ovarian lipid peroxidation. Administration of a luteolytic dose (3 microg kg(-1)
body weight i.p.) of a
synthetic PGF(2alpha) increased
thiobarbituric acid reactant content in ovaries from rats on day 9 of pseudopregnancy. As this effect was reversed partially by
L-NAME, it is proposed that during regression of corpora lutea,
PGF(2alpha) and NO are involved in regulation of lipid peroxidation. As this effect was only reversed partially, it is possible that there is another mechanism involving
PGF(2alpha) (but not the NO-NOS pathway) in regulation of ovarian lipid peroxidation. Furthermore, the administration of
PGF(2alpha) enhanced ovarian NOS activity, whereas
cyclooxygenase inhibition (by
indomethacin treatment in vivo) reduced it. As western blotting of ovarian homogenates obtained from PGF(2alpha)-injected rats increased inducible NOS (iNOS) content, it is concluded that
PGF(2alpha) enhances both activity and synthesis of NO in rat ovarian tissues during luteolysis. Taken together, these results indicate that in ovaries with regressing corpora lutea, both NO and
PGF(2alpha) are involved in part in regulation of lipid peroxidation.