Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology.
The human glucocorticoid receptor (GR) gene expresses two splicing isoforms alpha and beta through alternative use of specific exons 9alpha and 9beta. In contrast to the classic receptor GRalpha, which mediates most of the known actions of glucocorticoids, the functions of GRbeta have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRbeta. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRalpha-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GRbeta is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRbeta, its mechanisms of action, and its pathologic implications.
Kino
Tomoshige
T
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bldg. 10, Clinical Research Center, Rm. 1E-3140, 10 Center Drive MSC 1109, Bethesda, MD 20892-1109, USA. kinot@mail.nih.gov
Su
Yan A
YA
Chrousos
George P
GP
D017398:Alternative Splicing / Q000235:genetics / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000235:genetics; D004194:Disease / Q000209:etiology* / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology
D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta