Steroid Action on Gene Expression: Possible Roles of Regulatory Genes and Nuclear Acceptor Sites

There has been exciting progress in the understanding of the mechanism of action of steroid hormones. The structures and functions of the various receptor protein domains as well as the various domains of steroid-regulated genes, including steroid response elements, are currently being elucidated. The roles of transcription factors in the steroid-altered regulation of gene transcription are just being defined. The nature of the nuclear acceptor sites, i.e. nuclear-binding sites, for steroid receptors are under investigation. The composition, location, and function of these nuclear acceptor sites for steroid receptors is crucial for understanding the mechanism of steroid regulation of gene expression. Possible roles of specific, DNA-binding, chromatin proteins in these acceptor sites have been suggested. A very rapid action of steroids on the expression of proto-oncogenes that code for nuclear regulatory proteins has recently been described. Using this information, we have proposed a novel steroid action model utilizing "regulatory genes" whereby the steroids would rapidly alter the expression of regulatory genes (early genes) whose protein products would return to the nucleus to regulate the expression of structural genes (late genes). The latter would occur via binding of these regulatory proteins (e.g. transcription factors) to the steroid-regulatory elements neighboring these late genes. This model would explain many of the characteristics reported from many laboratories on the action of steroid hormones on gene expression.