Related Experiment Video
Updated: Jun 5, 2026

A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
Molecular determinants of hormone sensitivity in rainbow trout glucocorticoid receptors 1 and 2
Armin Sturm1, Louise Colliar, Michael J Leaver
1University of Stirling, Institute of Aquaculture, Stirling, Scotland, UK.
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.
Related Concept Videos
Intracellular Hormone Receptors
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Global Regulatory Systems
Target Cell Response to Hormones
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...

