Intrafollicular distribution of plasminogen activators and their hormonal regulation in vitro

Recent studies from our laboratory corroborated the suggested role of plasminogen activation in follicular rupture at ovulation, and its involvement in the activation process of collagenolysis in the follicle. In the present study, the molecular types and cellular source of plasminogen activator (PA) were examined. Explanted preovulatory follicles produced in vitro both urokinase type and tissue type (t-PA) activators. Upon gonadotropin stimulation a highly significant increase in t-PA, but not in urokinase type, was observed. Separation of the follicle into granulosa cells and residual tissue, mainly theca, revealed that both compartments produce both types of PA. The granulosa compartment was found to produce 80-90% of the total follicular PA activity. Gonadotropins stimulated predominantly t-PA. Most of the gonadotropin-enhanced PA activity produced by granulosa cells was secreted into the culture medium, whereas that from thecal origin remained in the tissue. Likewise, in whole follicles only about 10% of PA was secreted into the medium. Gonadotropin-induced PA activity in vitro was reduced by inhibitors of steroidogenesis. This inhibition was overcome by the addition of estradiol-17 beta. The inhibition of steroidogenesis affected predominantly the t-PA type of PA. In conclusion, the granulosa cells contribute most of the follicular PA activity, and t-PA is predominantly enhanced by gonadotropin and estrogen. It seems, therefore, that t-PA is the activator involved in the processes leading to follicular rupture.