Introduction

Steroid receptors are important determinants of endocrine disrupter consequences. As the most frequently proposed mechanism of endocrinedisrupting contaminant (EDC) action, steroid receptors are not only targets of natural steroids but are also commonly sites of nonsteroidal compound action. In fact, for many years, steroid receptor binding has been used as evidence of the endocrine-disrupting potential of a compound. Functional activation of steroid receptors has also been studied for years. Reporter assays such as the chloramphenicol acetyltransferase (CAT) assay have been used with both estrogen and androgen receptors (ERs and ARs) to test steroid receptor activation. In this review, significant factors from generalized steroid receptor interactions to species differences in steroid receptor sequences are explored in an effort to more fully discern the significance of EDC activation of steroid receptors. Interaction or “cross-talk” among growth factors, thyroid hormones, and natural hormones is considered in light of EDC ligands. Although this review concentrates on steroid receptors, the aryl hydrocarbon (Ah) receptor is discussed briefly due to its similarities to steroid receptors. Factors affecting the result of EDC/steroid receptor binding are then presented, beginning with a discussion of agonistic and antagonistic responses. This is followed by an exploration of the techniques used to assess receptor binding and contributions of accessory

proteins such as binding proteins and receptor-associated proteins. The importance of receptor changes is then examined with discussions of receptor translocation, receptor stabilization/dissociation, receptor dimers/heterodimers, and ligandinduced receptor conformational changes. Ontogenetic and phylogenetic receptor differences are then explored, including age, season, tissue, and speciesrelated differences. Finally EDC synergy and implications of environmental exposure are presented.