“…If we consider that the most potent stereoisomers were always the 3,8-bisquaternary members of each series, that change in this configuration causes a loss of potency of two to eleven times, and further that configurational change at the 17-position does not significantly affect potency, then one might postulate that interaction with the receptor at the 3-position is more important than interaction in either configuration at the 17-position. Thus our results would tend to support the adumbration theory of Loewe & Harvey (1952), who postulated a "one point" attachment theory, where the bulk of the molecule, in this case presumably the steroid nucleus, shields the receptor, rather than the suggestion of Cavallito &Gray (1960), andWaser (1959), that a two point receptor complex could be formed. The relatively flat steroid nucleus in the 5a-series may be a more effective shield than the more folded steroid nucleus of the 5/3-series, and therefore the 5a-series should be more potent than the corresponding members of the 5/3-series, which accords with our observations.…”