Diversity of glucocorticoid receptor signaling: molecular mechanisms and therapeutic implications

Viho, E.M.G. (2023)

Doctoral Thesis

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.

• Glucocorticoids
• Glucocorticoid receptor signaling
• Stress
• Hypothalamic Pituitary Adrenal (HPA) axis
• Nuclear receptors
• Transcriptome
• Genomics
• Cell diversity
• Protein interactions

• All authors: Viho, E.M.G.
• Supervisor: Meijer, O.C.
• Co-supervisor: Kroon, J.
• Committee: Heijmans, B.; Winter, E.M.; Zwart, W.; Dubois, V.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2023-09-07
• ISBN (print): 9789464589597
• Sponsorship: Corcept Therapeutics