Steroid receptors at the nexus of transcriptional regulation

During the past few years, our understanding of nuclear receptor action has dramatically improved as a result of the identification and functional ana lysis of co-regulators such as factors involved in chromatin remodeling, tr anscription intermediary factors (co-repressors and co-activators), and dir ect interactions with the basal transcriptional machinery. Furthermore, the elucidation of the crystal structures of the empty ligand-binding domains of the nuclear receptor and of complexes formed by the nuclear receptor's l igand-binding domain bound to agonists and antagonists has contributed sign ificantly to our understanding of the early events of nuclear receptor acti on. However, the picture of hormone- and hormone receptor-mediated mechanis ms of gene regulation remain incomplete and extremely complicated when one also considers the "nontraditional" interactions of hormone-activated nucle ar receptors, for example, interactions between the activated steroid recep tors and components of the chromatin/nuclear matrix; and finally the nongen omic effects that steroid hormones can exhibit with other signaling pathway s. In this prospectus on steroid receptors, we discuss the implications of various steroid hormone and nuclear receptor interactions and potential fut ure directions of investigation. (C) 1998 Wiley-Liss, Inc.