ANTI-ESTROGEN ASSAY OF NEUTRAL STEROIDS ADMINISTERED BY SUBCUTANEOUS INJECTION12

Abstract
A method for the evaluation of anti-estrogenic activity is described using 20–22-day old estrone stimulated female Swiss albino mice. Both the estronc and the test compound were injected subcutaneously but at separate sites. The end-point was the degree of inhibition of estrogen-produced uterine growth. The relative antiestrogenic potency of 26 steroids is reported on the basis of the minimum weight of compound needed to produce a statistically significant inhibition of the uterine stimulation produced by 0.4 μg. of estrone. Correlations of structure and activity may be summarized as follows: reduction of a Δ4-3-kcto group in ring A to a 5α-3-keto grouping produced an enhanced activity in testosterone but not in three other steroids studied; formation of the 19-nor steroid led to enormous increases in activity for 17α-ethyltcstosterone (62 times) and 17-ethynyltestosterone (31 times) but not in four other steroids of varied structures; and substitution of 17α-hydrogen by a methyl, ethyl, or ethynyl group usually produces a compound with increased anti-estrogenic activity.