In the ovary, cortisol is oxidized to cortisone by 11␤-hydroxysteroid dehydrogenase (11␤HSD). The present study investigated whether follicular fluid (FF) from large antral follicles and spontaneous ovarian cysts, isolated from bovine and porcine ovaries, contained modulators of 11␤HSD activity. Whereas FF from antral follicles had no significant effect over 1 h on NADP ؉ -dependent 11␤HSD activity in rat kidney homogenates, enzyme activity was inhibited by FF from bovine and porcine ovarian

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... ts (80.5% ؎ 2.3% and 72.8% ؎ 3.4% of control, respectively). Following C18 reverse-phase chromatography, the hydrophilic fractions of FF from bovine and porcine antral follicles stimulated NADP ؉ -dependent 11␤HSD activities (111.5% ؎ 21.6% and 55.2% ؎ 5.7% respectively). Hydrophobic compounds inhibited NADP ؉ -dependent cortisol oxidation by 58.2% ؎ 5.1% (bovine) and 45.7% ؎ 2.0% (porcine). In both species, FF from ovarian cysts appeared to contain less of the hydrophilic stimuli to 11␤HSD activity and more of the hydrophobic inhibitors. The FF from antral follicles and ovarian cysts, and the C18 fractions thereof, had no significant effect on NAD ؉ -dependent cortisol oxidation. The ovarian modulators of NADP ؉ -dependent 11␤HSD activities did not coelute with cortisol, cortisone, estradiol, testosterone, progesterone, pregnenolone, and cholesterol. However, the 11␤HSD stimuli in porcine FF from both antral follicles and cysts coeluted with prostaglandin (PG) E 2 and PGF 2␣ . We conclude that large antral follicles and spontaneous ovarian cysts, in both the cow and the pig, contain ovarian modulators of the NADP ؉ -dependent 11␤HSD activity. Moreover, FF from spontaneous ovarian cysts, because of decreased content of the 11␤HSD stimulus accompanied by increased content of the 11␤HSD inhibitors, exerts a net inhibitory effect on 11␤HSD activity. cortisol, follicle, ovulation, ovulatory cycle 1 Supported by a grant from Freemedic plc (London, U.K.), BBSRC project grant 48/S15850, and MRC Studentship G69/1756.