PT  - JOURNAL ARTICLE
AU  - Yoshinao Katsu
AU  - Satomi Kohno
AU  - Kaori Oka
AU  - Michael E. Baker
TI  - Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors
AID  - 10.1101/036665
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 036665
4099  - http://biorxiv.org/content/early/2016/01/14/036665.short
4100  - http://biorxiv.org/content/early/2016/01/14/036665.full
AB  - We investigated the evolution of the response of human, chicken, alligator and frog glucocorticoid receptors (GRs) to dexamethasone, cortisol, corticosterone, 11-deoxycorticosterone, 11-deoxycortisol and aldosterone. We find significant differences among these vertebrates in the transcriptional activation of their full length GRs by these steroids, indicating that there were changes in the specificity of the GR for steroids during the evolution of terrestrial vertebrates. To begin to study the role of interactions between different domains on the GR in steroid sensitivity and specificity for terrestrial GRs, we investigated transcriptional activation of truncated GRs containing their hinge domain and ligand binding domain (LBD) fused to a GAL4 DNA binding domain (GAL4 DBD). Compared to corresponding full length GRs, transcriptional activation of GAL4 DBD-GR hinge/LBD constructs required higher steroid concentrations and displayed altered steroid specificity, indicating that interactions between the hinge/LBD and other domains are important in glucocorticoid activation of these terrestrial GRs.