Gonadotropins regulate plasminogen activator production by rat granulosa cells

The role of FSH in the regulation of plasminogen activator production was studied in granulosa cells obtained from 23- to 25-day-old female rats. Cells cultured without FSH secreted a negligible amount of plasminogen activator. Purified ovine, rat, and human FSH produced dose-dependent increases in plasminogen activator production. This FSH effect was mimicked by analogs of cAMP, prostaglandin E2, and choleratoxin. Purified ovine LH and ovine PRL had no effect on plasminogen activator production by these immature granulosa cells. However, when these granulosa cells were treated in vitro or in vivo with FSH and then exposed to LH or PRL, the cells responded to LH in a dose-dependent manner with increased plasminogen activator production. These cells remained unresponsive to PRL. Similarly to FSH, in vitro pretreatment of the cells with choleratoxin or analogs of cAMP also induced responsiveness to LH with increased plasminogen activator production. This responsiveness to both FSH and LH with increased plasminogen activator production was also observed in granulosa cells obtained from rat preovulatory follicles. These studies demonstrate that: 1) FSH but not LH regulates plasminogen activator production by immature granulosa cells from preantral follicles; 2) Pretreatment of the undifferentiated granulosa cells with FSH, choleratoxin, or cAMP induced granulosa cell responsiveness to LH with increased plasminogen activator production; and 3) Granulosa cells obtained from preovulatory follicles respond to both FSH and LH with increased plasminogen activator secretion. These results suggest that with the LH surge at ovulation, plasminogen activator production in follicles is increased and may be important in follicular rupture.