Uterine plasminogen activator activity: Modulation by steroid hormones

We have used a sensitive and quantitative assay to investigate the hormonal regulation of plasminogen activator (PA) activity in the rat uterus. PA activity is increased 5-fold (per U protein or DNA) by low physiological (0.1 μg) doses of estradiol, with increases in activity first observed at approximately 12 h. The stimulation of PA activity shows strict specificity among the steroid hormones, being stimulated by estrogens only or by high doses of dihydrotestosterone, which are known to affect the estrogen receptor system, and this stimulation is suppressed markedly by triphenylethylene antiestrogens. Comparative dose-response studies with a variety of estrogens of different uterotropic potencies indicate a good correlation between the potencies of different estrogens in stimulating PA activity and uterine growth (diethylstilbestrol = 17β-estradiol < estrone = 17α-estradiol < estriol), with the exception of the zearalanol estrogen P-1496, which was consistently a potent stimulator of PA activity while being a very weak uterotropic agent. These studies suggest that increases in uterine PA levels may serve as a good marker of estrogen action in the uterus. Although the role of PA in uterine function remains unknown at present, its relatively large increase (up to 25-fold increase in content per uterus) may play a role in tissue remodeling during uterine growth.