Ten years after: reclassification of steroid-responsive genes

Abstract

Although several hundred genes are directly or indirectly regulated by steroid hormones, significant gaps exist in our understanding of the relevant mechanisms, particularly for those genes that do not directly bind intracellular receptors or that exhibit delayed changes in transcription rates upon receptor binding. To assist in defining the mechanism of action of steroid hormones, we are proposing that a standard nomenclature be adopted for classifying steroid-responsive genes, based upon whether the receptors directly bind to the target genes and the kinetics of the response. Three categories are proposed: primary response genes, delayed primary response genes, and secondary response genes.

Glucocorticoid receptor-mediated apoptosis: mechanisms of resistance in cancer cells

“…These include members of the p160 family of proteins (SRC1, PGC1, AIB1, etc.). Upregulation of transcription can usually be observed a few hours after the original Gc signal (Dean & Sanders 1996). GR can also upregulate gene transcription using mechanisms other than classical GREs; GR composite regulatory elements exist where GR interacts with DNA along with other transcription factors such as c-Myb (Geng & Vedeckis 2005) and the GR can also bind to other DNA-bound transcription factors, a process termed 'tethering', and modulate their effects as seen with the Gc-mediated regulation of mitogen-activated protein kinases (MAPK)-phosphatase 1 (DUSP1) transcription where the GR effect is modulated by binding to promoter bound C/EBPb (Johansson-Haque et al 2008).…”

Gene regulation by the glucocorticoid receptor: Structure:function relationship

“…This sequence of events is termed primary regulation. For the most part, genes that are under primary regulation show changes in transcriptional output in a few hours [4]. The sequence from steroid entry and binding to the receptor, to receptor reaching the nucleus takes only a few minutes.…”

Acute differential regulation by corticosteroids of epithelial sodium channel subunit and Nedd4 mRNA levels in the distal colon

“…Recent studies of sodium transport pathways have defined several potential sites of aldosterone action [15,38] which has stimulated a search for aldosterone-regulated genes. A putative aldosterone-induced increase in an mRNA level may be due to a primary effect of the MR on the regulatory region of that gene, or it may be a secondary effect whereby a primary response gene directly or indirectly mediates the observed change in mRNA level [9]. The early phase of the antinatriuretic response to aldosterone is seen within 3 h, usually by 60 min, so a candidate primary response gene should be induced within that time [38].…”