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.
Graduate School of Life Science, Hokkaido University, Sapporo, Japan; Department of Biological Sciences, Hokkaido University, Sapporo, Japan. Electronic address: ykatsu@sci.hokudai.ac.jp.
Yoshinao
Y
Katsu
Department of Obstetrics and Gynecology, Medical University of South Carolina, and Marine Biomedicine and Environmental Science Center, Hollings Marine Laboratory, Charleston, SC, USA.
Satomi
S
Kohno
Graduate School of Life Science, Hokkaido University, Sapporo, Japan.
Kaori
K
Oka
Department of Medicine, University of California, San Diego, CA, USA. Electronic address: mbaker@ucsd.edu.
Michael E
ME
Baker
D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000489:Alligators and Crocodiles; D000494:Allosteric Regulation; D000818:Animals; D001001:Anura; D002645:Chickens; D019143:Evolution, Molecular; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D011965:Receptors, Glucocorticoid
Alligator; Allosteric regulation; Chicken; Glucocorticoid evolution; Glucocorticoid receptor; Xenopus