Induction and inhibition of uterine vasodilation by catechol estrogen in oophorectomized, nonpregnant ewes

The biological activity of the catechol estrogens remains in question. The effect of these substances on uterine blood flow, another measure of estrogenicity, has not been evaluated. In this investigation we studied the effect of catechol estrogens on uterine blood flow in six chronically instrumented, oophorectomized, nonpregnant ewes. Electromagnetic flow probes were implanted around the main uterine arteries and catheters were placed in distal branches of the uterine arteries to provide direct access to the uterine circulation. Dose-response curves were constructed that described the magnitude of estrogen- induced uterine vasodilation after the local, intraarterial infusion of 17β-estradiol (E₂), estrone (E₁), 2-hydroxyestradiol (2-OHE₂), and 2-hydroxyestrone (2-OHE₁). Significant increases in uterine blood flow were observed after the infusion of each estrogen. The order of potency was E₂ < E₁ < 2-OHE₂ < 2- OHE₁; the doses of 2-OHE₂ and 2-OHE₁ necessary to obtain a response comparable to that seen with E₂ were estimated to be 62.5 and 500 times greater, respectively. The characteristics of the blood flow responses were similar with all four estrogens studied. After the infusion of the catechol estrogens, inhibition and/or blunting of the E₂-induced uterine vasodilation was observed for up to 1 week. This did not occur after the administration of either E₂ or E₁. From the results of these studies, it is evident that both 2-OHE₂ and 2-OHE₁ are biologically active estrogens, albeit weak, and these substances also may act as antiestrogens via competitive inhibition.