Estrogen-like Effect of Chelating Agents on Rat Uterine Phosphorylase Activity

Abstract

An injection of ethylenediaminetetraacetic acid (EDTA) increased phosphorylase a activity in uteri of spayed rats within 1 hr, an effect similar to that produced by estradiol after 48 hr. Phosphorylase a activity was also increased by the addition of EDTA to the homogenates of uteri from spayed rats. The effect of EDTA was duplicated with 8-hydroxyquinoline (sulfate). Phosphorylase a activity in uteri from estrogenprimed rats was increased in vivo and in vitro in the presence of EDTA, but to a lesser extent because of the initially higher enzyme activity. Analysis of the effect of EDTA revealed that the chelating agent was unable to increase the activity of partially purified uterine phosphorylase or of the supernatant fraction of homogenates centrifuged at 100 × μ for 30 min at O C. Reconstitution of the whole tissue homogenate permitted the EDTA effect to be manifested. No evidence was found for the involvement of cyclic 3',5'-AMP in the increase in phosphorylase a activity. The effect of EDTA in vivo upon phosphorylase activity of skeletal muscle, liver and ductus deferens of the rat is included for comparative purposes. The increase of phosphorylase a activity by EDTA was not demonstrable in uteri from several other mammalian species. A tentative mechanism for the effect of chelating agents on rat uterine phosphorylase activity is presented (Endocrinology76: 491, 1965)