The evolution, structure and function of the ray finned fish (Actinopterygii) glucocorticoid receptors

Abstract

Please cite this article as: Bury, N.R., The evolution, str uctur e and function of the r ay finned fish (Actinopter ygii) glucocor ticoid r eceptor s, General and Comparative Endocrinology (2016), doi: http:// dx.doi.org/10. 1016/j.ygcen.2016.06.030 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. split from the basal ray-finned fish resulted in 2 GRs: one GR group, GR1, has retained the 9 20 amino acids insert whereas the other group, GR2, has not. The exception to this is the 21 zebrafish, that have lost one of the GRs, but they do possess 2 GRs with a splice variant 22 that lacks the C-terminal portion of the GR to form GRβ which acts as a dominant-repressor 23 of the wildtype GR. Another splice variant sees the basal ray-finned GR and teleost GR1 24 without the 9 amino acids insert. The molecular basis for GRs retention is beginning to be 25 unravelled. In Pantadon buchholzi, rainbow trout, carp, marine and Japanese medaka GR2 26 is more sensitive to glucocorticoids (GC), thus potentially playing a more significant role in 27 regulating gene expression at basal circulatory GC concentrations. However, this division in 28 GC sensitivity is not seen in other species. The few studies to evaluate the significance of 29 the 9 amino acid insert have shown that it affect maximal transactivational activity the extent 30 to which is dependent on the number of glucocorticoid response elements (GREs) present in 31 the reporter plasmid. The retention of these GRs would suggest there was an evolutionary 32 advantage, which saw the development of a complex regulatory process to mediate the 33 actions of the glucocorticoids. 34

Early-life social environment alters juvenile behavior and neuroendocrine function in a highly social cichlid fish

“…Receptor has subtypes 1a and 1b, which differ by a nine amino acid insertion between the two zinc fingers in the DNA-binding domain (Bury, 2017;Greenwood et al, 2003;Korzan et al, 2014). These receptors differ substantially in their affinity for cortisol.…”

“…In adult A. burtoni, MR is 100-fold more sensitive to cortisol than the GRs and is likely to be occupied with cortisol at basal levels (in fish and tetrapods). GR2 has the next highest sensitivity, followed by GR1a, then GR1b (Arterbery et al, 2011;Bury, 2017;Greenwood et al, 2003). Changes in HPA/I axis function typically manifest as altered baseline levels of circulating glucocorticoids, a higher or lower glucocorticoid 'peak' in response to an acute stressor, and/or altered efficiency of the negative feedback loop that returns the system to baseline.…”

Annotation of the Nuclear Receptors in an Estuarine Fish species, Fundulus heteroclitus

“…In addition, medaka, stickleback ( Gasterosteus aculeatus ), common carp ( Cyprinus carpio ) and rainbow trout ( Oncorynchus mykiss ) all have two GRs (97,98); however, rainbow trout and common carp have undergone an additional round of genome duplication that may explain why these species have two GRs. Zebrafish ( Danio rerio ), only has one GR, GR2, that is missing a 9 amino acid sequence between the zinc fingers of the DBD (98,99).…”

“…Zebrafish ( Danio rerio ), only has one GR, GR2, that is missing a 9 amino acid sequence between the zinc fingers of the DBD (98,99). It is interesting to speculate that the increase in GRs are crucial in salt balance, especially in marine or estuarine species (12,100,101) as GR regulates salt balance in part by regulating the transcription of the sodium-chloride cotransporter and sodium-potassium ATPase (102,103).…”

Early-life social environment alters juvenile behavior and neuroendocrine function in a highly social cichlid fish

“…Many 644 actually decrease efficiency. Juvenile stress physiology should be tested directly because 668 negative feedback mechanisms are complex and involve multiple receptors (Bury, 2017;669 Kiilerich et al, 2018). Overall, little is known about the differential roles of GR1a and GR1b, 670 and the differences that have been demonstrated appear to be species-specific (Bury, 2017).…”