Glucocorticoids Stimulate Plasminogen Activator Production by Rat Granulosa Cells*

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Abstract
We studied the direct effects of glucorticoids on plasminogen activator (PA) production by rat granulosa cells. PA production was assayed by culturing rat granulosa cells on [125I]fibrin plates and determining the extent of fibrinolysis after addition of the specific substrate plasminogen. In granulosa cells from preantral follicles of immature rats, treatment with FSH caused dose-dependent increases in PA production whereas glucocorticoids by itself was without effect. Increasing concentrations (10-10 to 10-6 M) of both natural and synthetic glucorticoids potentiated the stimulating effect of FSH on PA production by 120 to 170%. The stimulatory potencies of the natural corticosteroids correlated with the glucocorticoid potencies (cortisol/corticosterone > aldosterone/11-deoxycorticosterone). In granulosa cells from Graafian follicles of mature rats, glucocorticoids on its own had direct stimulating effect on PA production. The stimulatory action of glucocorticoids on FSH-dependent PA production was completely blocked by simultaneous treatment with antiglucocorticoid RU 486. Antiserum directed against tissue-type PA (tPA) neutralized the increased fibrinolytic actions of glucorcorticoids. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography techniques, we showed that the increase in fibrinolytic activity in response to glucocoticoids resulted from increased production of tPA rather than urokinase-like PA. The effect of glucocorticoids on the production of PA inhibitors (PAI) was examined by 1) neutralization of urokinase activity by increasing amounts of culture media from granulosa cells treated with glucocorticoids, 2) reverse fibrin autography, and 3) Western blot analysis with a specific PAI antiserum. All these methods failed to detect a stimulatory action of glucocorticoids, with or without FSH, on PAI production by rat granulosa cells in the culture media. Our data showed that glucocorticoids have a direct stimulating effect on tPA production, but unlike its action on other in vitro systems, they have no significant effect on PAI production by rat granulosa cells in vitro.