Tumor necrosis factor alpha inhibits rat granulosa cell plasminogen activator activity in vitro during follicular...

The objective of the present in vitro study was to examine the potential modulatory influence of tumor necrosis factor-alpha (TNF alpha) on the granulosa cell plasminogen activator (PA) system during follicular development. Undifferentiated and differentiated rat granulosa cells of preantral follicles and antral follicles, respectively, were cultured in a chemically defined medium with or without TNF alpha and in the absence or presence of FSH (400 ng/ml). TNF alpha (0.5-50 ng/ml) inhibited basal and FSH-induced net PA activities in cultures of granulosa cells from preantral and antral follicles in a concentration- and time-dependent manner. Although PA activities with corresponding molecular masses of 55 kDa and 30 kDa (tissue-[tPA] and urokinase-[uPA] type PA, respectively) were observed in culture of undifferentiated granulosa cells, only tPA was detectable in differentiated cells. Concomitant to the stimulation in PA activities by FSH was a marked increase in progestin secretion and a decrease in DNA synthetic capacity at both stages of follicular development. Independent of the differentiative state of the granulosa cells, TNF alpha suppressed FSH-stimulated tPA activity, but potentiated FSH-induced uPA activity in undifferentiated granulosa cells. The inhibition of the gonadotropin action by TNF alpha was accompanied by an increase in PA inhibitor activity, which was more pronounced in cultures of differentiated granulosa cells. TNF alpha inhibited FSH-induced progestin secretion and reversed the action of the gonadotropin on DNA synthesis irrespective of stage of follicular maturation. These studies demonstrate that TNF alpha modulates gonadotropic action on granulosa cell differentiation (PA and progestin secretion) and proliferation (DNA synthesis) during follicular development.(ABSTRACT TRUNCATED AT 250 WORDS)