Glucocorticoid receptor isoforms generated by alternative splicing and alternative translation initiation

Abstract

The glucocorticoid hormone receptor (NR3C1) is the transcription factor that controls a large variety of physiological processes in mammals. According to modern estimates, the glucocorticoid receptor participates in regulation of the expression of thousands of genes; however, the sets of glucocorticoid-controlled genes in different cell types are different. At the same time the amplitude, directivity, and time- and dose-dependence of the hormone response are broadly variable both for the same gene in different cell types and for different genes in the same cell. Such specificity of a glucocorticoid receptor is determined, on the one hand, by architecture of regulatory regions of target genes, and on the other hand, by the complexity of the glucocorticoid receptor gene. The gene has nine alternative promoters and produces numerous protein isoforms as a result of alternative splicing and alternative translation initiation. This review summarizes the current knowledge on glucocorticoids receptor isoforms and mechanisms of their formation.