From an evolutionary perspective, stress is an adaptive system that is necessary togenerate appropriate responses to stochastic and unpredictable events, and copeaccordingly with the environment.... Show moreFrom an evolutionary perspective, stress is an adaptive system that is necessary togenerate appropriate responses to stochastic and unpredictable events, and copeaccordingly with the environment. The physiological response to stress has beenremarkably conserved in vertebrate evolution. However, the threats to ourinternal “equilibrium” have changed between our ancestral environments and ourcurrent modern societies, and the demands for survival have evolved. Theglucocorticoid receptor (GR) is a timeless component of stress adaptation, as it is atthe intersection between the environmental stressors (i.e., physical, or psychosocial)and the genome. Therefore, the GR represents a valuable therapeutic target instress- and glucocorticoid-related disorders. This thesis provides new insightsinto the molecular mechanisms underlying GR signaling in metabolic diseases andbrain function and highlights the promise and importance of selectivity in novel GRtargeting treatments. Show less
