The Structure and Function of Oestrogens. VI The Quinone Methide Hypothesis: Stability of the Benzylic Hydrogen Atoms of meso-Hexoestrol during Oestrogenic Stimulation in Mice

Abstract

A new hypothesis for oestrogen action at the molecular level is that the phenolic moiety of an oestrogen is oxidized to the corresponding quinone methide which is rapidly reduced with, say, NADPH to regenerate the oestrogen; the feedback from the rapid consumption of oxidant and/or reductant in the target organs might be responsible for the local increase in RNA synthesis, and its consequent phenomena. This hypothesis requires continuous removal and replacement of a benzylic hydrogen atom (H9oc of oestradiol) in an oestrogen at the receptor site. When a physiological dose of a mixture meso-(2-'4C)- and meso-(2,3,4,5-3H4 )hexoestrol was administered intravaginally in mice, the 14C: 3H ratio in the phenolic portion of the vaginal extracts was essentially the same as that of the pure test mixture. This indicates that there was no net exchange of benzylic hydrogen in meso-hexoestrol during its stimulation of the mouse vagina.