Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promoter-specific action of these hormones.

Abstract

The selective action that steroid hormones and the hormones for the other nuclear receptors have in different tissues and on different responses is well known. In fact, this recognized selectivity forms the basis for major efforts, currently underway in the pharmaceutical industry and at universities, toward the development of new, synthetic hormones whose profile of desired activities is optimized for specific therapeutic and preventative applications. This commentary will examine the pharmacological mechanisms that underlie this selectivity. The study of steroid hormone pharmacology poses particular challenges. In viva, many steroids have pleiotropic activity, displaying a variety of effects in different tissues. Even in cell-based in vitro systems, attempts to investigate the molecular basis for steroid hormone action and the selectivity of this action are confounded by the fact that the genomic responses elicited by these ligands can be both primary and secondary (Le. cascade) responses. In the latter situation, the correlation between molecular interaction and response is complex and indirect; this makes it difficult to clearly determine what interactions define the pharmacological parameters of potency and bio-