Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors.
We investigated the evolution of the response of human, chicken, alligator and frog glucocorticoid receptors (GRs) to dexamethasone, cortisol, cortisone, 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.
['Katsu|Yoshinao|Y|', 'Kohno|Satomi|S|', 'Oka|Kaori|K|', 'Baker|Michael E|ME|']
D000305:Adrenal Cortex Hormones D000489:Alligators and Crocodiles D000494:Allosteric Regulation D000818:Animals D001001:Anura D002645:Chickens D019143:Evolution, Molecular D006801:Humans D011965:Receptors, Glucocorticoid
Chicken Alligator Glucocorticoid receptor Allosteric regulation Glucocorticoid evolution Xenopus