NOVEL INVITRO METHOD FOR DEMONSTRATING PRO-ESTROGENS - METABOLISM OF METHOXYCHLOR AND O,P'DDT BY LIVER-MICROSOMES IN THE PRESENCE OF UTERI AND EFFECTS ON INTRACELLULAR-DISTRIBUTION OF ESTROGEN RECEPTORS

A method for demonstrating proestrogens in vitro has been developed. The method involves the incubation of the potential proestrogen with liver microsomes and NADPH in the presence of rat uteri, followed by examination of the effects of metabolism of the compound on the distribution of uterine estrogen receptor (R) in the cytosol (Rc) and in the nucleus (Rn). Thus, we examined whether DDT derivatives, which possess estrogenic activity in vivo, exhibit pro-estrogenic properties in vitro. Using this method, it appears that methoxychlor is a proestrogen, since the presence of microsomal enzymatic activity is required for methoxychlor to elicit translocation of uterine Rc into the nucleus, namely, the lowering of Rc and elevation of Rn. By contrast, o,p'DDT was active per se in translocating Rc and did not require the presence of microsomal enzymes for activity. © 1979.