Corticosteroid-binding globulin levels in North American sciurids: implications for the flying squirrel stress axis

Corticosteroid-binding globulin (CBG) helps to regulate tissue bioavailability of circulating glucocorticoids (GCs), and in most vertebrates, ≥80%–90% of GCs bind to this protein. New World flying squirrels have higher plasma total cortisol levels (the primary corticosteroid in sciurids) than most vertebrates. Recent research suggests that flying squirrels have either low amounts of CBG or CBG molecules that have a low binding affinity for cortisol, as this taxon appears to exhibit very low proportions of cortisol bound to CBG. To test whether CBG levels have been adjusted over evolutionary time, we assessed the levels of this protein in the plasma of northern (Glaucomys sabrinus (Shaw, 1801)) and southern (Glaucomys volans (Linnaeus, 1758)) flying squirrels using immunoblotting, and compared the relative levels among three phylogenetically related species of sciurids. We also compared the pattern of CBG levels with cortisol levels for the same individuals. Flying squirrels had higher cortisol levels than the other species, but similar levels of CBG to their closest relatives (tree squirrels). We conclude that CBG levels in flying squirrels have not been adjusted over evolutionary time, and thus, the uncoupling of CBG levels from cortisol concentrations may represent an evolutionary modification in the lineage leading to New World flying squirrels.