Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GR alpha and GR beta, generated through alternative splicing mechanisms. While GR alpha is the classic receptor responsible for GC actions, GR beta has been implicated in the impairment of GR alpha-mediated activities. Interestingly, in contrast to the popular belief that GR beta actions are restricted to its dominant-negative effects on GR alpha-mediated responses, GR beta has been shown to have intrinsic activities and directly regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GR alpha-independent manner. Furthermore, GR beta has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GR beta-mediated responses, with a focus on the GR alpha-independent/intrinsic effects of GR beta and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

Automated summary

This passage discusses how glucocorticoids act through the GR receptor to produce different cellular responses throughout the body and the different effects of GRα and GRβ on the human body.