The oestrogenic and anti-oestrogenic properties of ring methyl-substituted stilboestrols

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Abstract
3,3′,5,5′-Tetramethylstilboestrol (I) and its α,α′-dimethyl- (II) and α,α′-diethyl- homologues (III) have been tested for oestrogenic and anti-oestrogenic activity. α,α′-Diethyl-3,3′,5,5′-tetramethylstilboestrol (III), by the uterine weight assay in immature mice, is 2·1 times 10−4 times as potent as an oestrogen as 17β-oestradiol [fiducial limits (0·95) = 1·59 times 10−4 −2·74 times 10−4] but 3,3′,5,5′-tetramethylstilboestrol (I) and α,α′,3,3′,5,5′-hexamethylstilboestrol (II) were oestrogenically inactive at a dose of 0·8 mg. Compound III exhibited auto-inhibition of its own oestrogenic response at doses between 1·8 and 7·2 mg. None of the compounds tested inhibited the uterotrophic response to 17β-oestradiol. Compounds II and III, but not compound I, produced a highly significant inhibition of the vaginal cornification response to 17β-oestradiol when the test compounds (5 μg) and 17β-oestradiol were administered intra-vaginally in a single solution. It is suggested that the compounds II and III compete with 17β-oestradiol for the oestrogen receptor and that methyl groups positioned ortho to the phenolic hydroxyl group sterically interfere with the binding of the compounds to the oestrogen receptor, or with the initiation of the oestrogenic response, or both.