Abstract
Conventional studies of steroid hormone action proceed via quantitation of the maximal activity for gene induction at saturating concentrations of agonist steroid (i.e., A(max)). Less frequently analyzed parameters of receptor-mediated gene expression are EC(50) and PAA. The EC(50) is the concentration of steroid required for half-maximal agonist activity and is readily determined from the dose-response curve. The PAA is the partial agonist activity of an antagonist steroid, expressed as percent of A(max) under the same conditions. Recent results demonstrate that new and otherwise inaccessible mechanistic information is obtained when the EC(50) and/or PAA are examined in addition to the A(max). Specifically, A(max), EC(50), and PAA can be independently regulated, which suggests that novel pathways and factors may preferentially modify the EC(50) and/or PAA with little effect on A(max). Other approaches indicate that the activity of receptor-bound factors can be altered without changing the binding of factors to receptor. Finally, a new theoretical model of steroid hormone action not only permits a mechanistically based definition of factor activity but also allows the positioning of when a factor acts, as opposed to binds, relative to a kinetically defined step. These advances illustrate some of the benefits of expanding the mechanistic studies of steroid hormone action to routinely include EC(50) and PAA.