Molecular determinants of hormone sensitivity in rainbow trout glucocorticoid receptors 1 and 2

Abstract

Please cite this article as: Sturm, A., Colliar, L., Leaver, M., Bury, N.R., Molecular determinants of hormone sensitivity in rainbow trout glucocorticoid receptors 1 and 2, Molecular and Cellular Endocrinology (2010), doi:10.1016/j.mce.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Dexamethasone modulates expression of genes involved in the innate immune system, growth and stress and increases susceptibility to bacterial disease in Senegalese sole (Solea senegalensis Kaup, 1858)

“…In this study, we used DXM to mimic the physiological and cellular responses produced by the natural glucocorticoid cortisol. DXM usually displays a similar or even higher glucocorticoid potency and affinity to both GRs than cortisol [1,28,37,50]. Our results demonstrate a direct effect of glucocorticoids on important productive parameters in sole reducing growth and increasing susceptibility to the pathogen Ph.…”

“…The goal of present work was to demonstrate a causal relationship between corticosteroids and the immunocompetence status of Solea senegalensis and their effects on the expression of a wide set of genes involved in innate immune system (g-type lysozyme and hamp1), HPI axis (crf, crfbp, pomca, pomcb, gr1 and gr2), HPT axis (thyroglobulin (tgb)), cellular stress defense system (hsp70 and hsp90aa), GH/IGF axis (igf-I and igf-Ir) and the neuropeptide trh. For that purpose, we selected the glucocorticoid DXM, a potent corticosteroid synthetic analogue with a high affinity to bind GRs and able to trigger corticosteroid-specific mediated cellular responses [28,37,38]. For easy management, immersion experiments using benthic postlarvae (three weeks after hatching) were performed.…”

Evolution of corticosteroid specificity for human, chicken, alligator and frog glucocorticoid receptors

“…Our data indicate that there were significant changes in the response to Cortisol and corticosterone are physiological glucocorticoids in terrestrial vertebrates and ray-finned fish [12,67,74]. Cortisone is a metabolite of cortisol, in which the C11-alcohol is metabolized to a ketone.…”

Evidence for a divergence in function between two glucocorticoid receptors from a basal teleost

“…Both PbGR1 and PbGR2b were unresponsive to aldosterone (data not shown). PbGR2a, which differs from PbGR2b by the presence of a nine-amino acid insertion into the C-domain, was not tested, as we have shown previously, by the analysis of numerous domain-swap mutants between rat GR and rainbow trout GR1 and GR2, the C-domains of which differ by the presence or absence of similar insertions, that this region of the receptor does not affect hormone sensitivity in our transactivation assay system [26,27]. Transactivation activity EC50 values could only be calculated for cortisol, 11-deoxycortisol, and corticosterone in PbGR2b, and cortisol and 11-deoxycortisol in PbGR1 (Table 1 and Figure 4 B - D).…”

“…Since the discovery of duplicated GRs in a number of teleost fish various studies have investigated the molecular characteristics, tissue expression patterns and functional traits (e.g., hormone binding or transactivation activity sensitivities) of each paralogue in an attempt to explain potential mechanisms by which the two GRs where retained [15,17-20,26-34]. However, probably because these studies have focused on the GRs of species that belong to advanced teleosts groups that emerged many millions of years after the teleost WGD event it has proven difficult to identify any unifying functional traits of each teleost GR [15,17-20,26-34]. For example, EC50 values at which hormones induce half-maximal stimulation of receptor transactivation activity reveal distinct differences in sensitivity between duplicated GRs of rainbow trout [19], but not Astatotilapia burtoni [15].…”