Effect of ovarian steroids on pharmacokinetics of Tergurid in rat uterus

The incorporation of 3H-17-beta-estradiol (3H-E2) and 3H-Tergurid (3H-Te) in the uteri of sexually immature rats was monitored for 16 hours following the treatment of the animals with Tergurid, a semisynthetic ergot alkaloid [acid maleate of N-(D-6-methyl-8-isoergolin-I-yl)-N',N'-diethylurea; VUFB-6638]. The differences in the incorporation of 3H-Te in relation to the presence of ovarial steroids (E2 and progesterone) were investigated for the same period in adult ovariectomized rats. In all the time intervals under study, the average values of 3H-E2 activities in the uteri of juvenile rats treated with Tergurid were lower than in the controls. This decrease was statistically significant (P<0.05) eight hours after treatment. The time course of the incorporation of 3H-Te in the uteri of the experimental and control animals was similar. The activities of incorporated 3H-Te in the uteri of adult rats treated with E2 were higher in all the intervals, the difference being statistically significant after two hours and 16 hours (P<0.05) and after four hours (P<0.01). Progesterone did not induce any significant differences in the incorporation of 3H-Te. These results suggest that the increased incorporation of Tergurid in the uteri of adult rats is due to a direct influence of E2. It was demonstrated by trials on juvenile rats that Tergurid does not combine with estrogenic receptors. As suggested by the decreased weights of the uteri of juvenile rats treated with Tergurid, the uterine cells are unable to react to exogenous administration of E2. In adult ovariectomized rats, the increased weights of uteri after Tergurid administration testify to a synergetic action with E2. (author)