Backgroung

After stress exposure, prolonged or excessive exposure to glucocorticoids has been consistently related to increased vulnerability to psychopathologic disorders (Zalachoras, 2013). Therefore, glucocorticoid receptor (GR) antagonism was predicted to have considerable therapeutic value in stress-related psychopathologies (De Kloet, 2005). Unlike full GR agonists or antagonists, selective glucocorticoid receptor modulators (SGRMs) are ligands that combine agonistic and antagonistic properties and are thereby able to separate beneficial from harmful treatment effects (Zalachoras, 2013). GR transcription specificity of the SGRMs is supported by the diversity of recruited coregulatory factors. CORT118335 and CORT108297 are two SGRMs that lead to opposite consequences on memory consolidation.

Objectives and Hypotheses

In this project we compared the GR co-regulators recruitment profiles of CORT118335 and CORT108297. We expect that respectively the antagonistic and agonistic properties are reflected by coregulatory interactions.

Methods

Coregulatory factors recruitment profiles were obtained using the MARCoNI technology.

Results

CORT118335 and CORT108297 differ significantly in their recruitment profile for 17/67 co-regulators. CORT118335 preferentially recruited 4, particularly the CREB Binding Protein (CBP). CORT108297 preferentially recruited 13 co-regulators at the GR, including Nuclear Receptor Coactivators (NCOA) 2, 3 and 6.

Conclusion

Differences in coregulatory recruitment could underlie the differential effects of CORT118335 and CORT108297 on memory consolidation.