Glucocorticoid Receptors and the Control of Gene Expression

Abstract

Steroid hormones mediate physiological responses in target cells via an interaction with specific, high-affinity receptors. Binding of hormone to these receptors results in a structural alteration in the receptor protein, allowing the steroid-receptor complex to bind tightly to acceptor sites within the nucleus (for reviews see Yamamoto and Alberts, 1976; Ringold, 1985). The association of steroid-receptor complexes with specific DNA sequences in the 5’ flanking regions of target genes such as those encoding the mouse mammary tumor virus (MMTV) (Payvar et al., 1983; Scheidereit et al., 1983), chicken lysozyme (Renkawitz et al., 1984), and human metallothionein-IIa (hMT-IIa) (Karin et al., 1984) appears to be important for transcriptional activation of their respective promoters. However, the detailed mechanisms by which glucocorticoids regulate specific gene expression remain hazy, largely owing to our poor understanding of receptor structure and receptor interactions with the transcriptional apparatus. Moreover, many genes appear to be regulated in a complex fashion in which regulatory mechanisms distinct from direct transcriptional activation by the steroid-receptor complex may be involved. Lastly, the basis for the tissue-specific expression of a constellation of steroid-responsive genes observed within a particular cell type remains to be elucidated.