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