Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/7613
Appears in Collections:Aquaculture Journal Articles
Peer Review Status: Refereed
Title: Molecular determinants of hormone sensitivity in rainbow trout glucocorticoid receptors 1 and 2
Authors: Sturm, Armin
Colliar, Louise
Leaver, Michael
Bury, Nicholas R
Contact Email: m.j.leaver@stir.ac.uk
Keywords: Steroid receptors
Teleost Fish
Cortisol
Stress response
Activation function 2
Ligand binding domain
Issue Date: 20-Feb-2011
Publisher: Elsevier
Citation: Sturm A, Colliar L, Leaver M & Bury NR (2011) Molecular determinants of hormone sensitivity in rainbow trout glucocorticoid receptors 1 and 2, Molecular and Cellular Endocrinology, 333 (2), pp. 181-189.
Abstract: Many teleost fish possess two glucocorticoid receptors (GR). In the rainbow trout rtGR1 and rtGR2 differ in their affinities to dexamethasone and EC50 values for glucocorticoids in transactivation assays, with rtGR2 being more sensitive. The objective of this study was to identify the molecular traits underlying the sensitivity difference. Domain-swap mutants between rtGR1 and rtGR2 showed that sensitivity was mainly determined by the hormone binding domain (E-domain). Chimeras exchanging three E-domain subregions indicated that all subregions influenced sensitivity, with the most C-terminal region that included AF2 having the greatest (12.6-fold) effects on cortisol transactivation EC50. The C-terminal extremity (CTE) in rtGR1 departs from a consensus preserved in other GRs. Introducing the consensus CTE into rtGR1 provoked a 4.2-fold decrease in transactivation EC50, suggesting CTE is one of several determinants of rtGR1's hyposensitivity. GRs with similar unusual CTEs exist in other salmonids, suggesting hyposensitive GR have evolved in this highly successful teleost lineage.
Type: Journal Article
URI: http://hdl.handle.net/1893/7613
URL: http://www.sciencedirect.com/science/article/pii/S0303720711000025
DOI Link: http://dx.doi.org/10.1016/j.mce.2010.12.033
Rights: The publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.
Affiliation: Aquaculture
University of Stirling
Aquaculture
King's College London

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