Diversity of glucocorticoid receptor signaling: molecular mechanisms and therapeutic implications

Abstract

From an evolutionary perspective, stress is an adaptive system that is necessary to

generate appropriate responses to stochastic and unpredictable events, and cope

accordingly with the environment⁠. The physiological response to stress has been remarkably conserved in vertebrate evolution⁠. However, the threats to our internal “equilibrium” have changed between our ancestral environments and our current modern societies, and the demands for survival have evolved⁠. The glucocorticoid receptor (GR) is a timeless component of stress adaptation, as it is at the intersection between the environmental stressors (i⁠.e⁠., physical, or psychosocial) and the genome⁠. Therefore, the GR represents a valuable therapeutic target in stress- and glucocorticoid-related disorders⁠. This thesis provides new insights into the molecular mechanisms underlying GR signaling in metabolic diseases and brain function and highlights the promise and importance of selectivity in novel GR targeting treatments⁠.