Interaction of Steroid Hormone Receptors with the Transcription Initiation Complex

I. IntroductionREGULATION of gene expression by steroid hormones is a traditional field of molecular endocrinology. The hormones act by binding to intracellular receptors, which themselves orchestrate the transcriptional response. After the cloning of the hormone receptors and the identification of their target sequences on DNA at the end of the 1980s, the question of how steroid hormones modulate the activity of various genes in target cells seemed to be solved. It was clear that steroid hormone receptors are ligand-activated transcriptional modulators, which in most cases act through binding to specific sequences on DNA called hormone-responsive elements (HREs) (1). Careful mutational analysis identified a modular structure of the receptors composed of a DNA-binding domain, nuclear localization signals, a ligand-binding domain, and several transactivation domains (2). Interactions of the receptors with components of the basal transcriptional machinery and with sequence-specific transcription factors were assumed to mediate their transcriptional effects. The prevalent opinion was that the mechanism of action of steroid hormones was a closed chapter ready for the textbooks and what remained to be done to complete the picture was merely the collection of details.