Characterization of the kinin system in the ovary during ovulation in the rat

Abstract

Ovulation has been noted for some time to bear a remarkable similarity to an inflammatory response. One of the principal components that is activated and helps mediate the events during an inflammatory response is the kinin system. Therefore, the purpose of the present study was to examine whether this system could be similarly activated and involved in the cascade of events that leads to ovulation. To answer this question, immature 23-day-old female rats were primed with eCG (10 IU) and ovulation was induced by administration of hCG (10 IU) 48 h later. Groups of rats were killed at 0 h, 10 h, 20 h, and 30 h after hCG for determination of ovulation, ovarian steroid levels, and changes in the levels of kinin system components. Plasma total kininogen levels did not change during the entire period studied. In contrast, ovarian total kininogen levels rose from 0 h to reach a peak at 10 h-a time immediately preceding the beginning of ovulation-after which the levels fell at 20 h, only to rise again at 30 h. Three species of kininogens, high molecular weight (HMW), low molecular weight (LMW), and T-kininogen, were shown to be present in the ovary. T-kininogen was the major kininogen present in the ovary, accounting for 60-92% of the total kininogen at any given time point during the ovulatory process. HMW kininogen levels accounted for only 1.2% of the total ovarian kininogen. The elevation in total ovarian kininogen levels at the 10-h time point was due to an increase in T-kininogen alone. T-kininogen remained significantly elevated at 20 h and 30 h. Conversely, ovarian LMW-kininogen levels fell at the 10-h and 20-h time points, only to rise again at 30 h. The activity of the cysteine protease, cathepsin B, was found to be suppressed at the 10-h time point after hCG. This suppression could be due to the rise in T-kininogen at this time, since T-kininogen is a potent cysteine protease inhibitor. Ovarian kallikrein activity was found to be high at 0 h, followed by a rapid fall to basal values at 8-30 h. In contrast, T-kininogenase activity was not detectable in either the ovary or plasma. These findings, as a whole, raise the possibility that the kinin system may be an important component in the cascade of events that leads to ovulation in the rat.