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A Chemical Screening Procedure for Glucocorticoid Signaling with a Zebrafish Larva Luciferase Reporter System
Published on: September 10, 2013
High blood cortisol levels and low cortisol receptor affinity: is the chub, Leuciscus cephalus, a cortisol-resistant
T G Pottinger1, T R Carrick, A Appleby
1Windermere Laboratory, NERC Centre for Ecology and Hydrology, The Ferry House, Ambleside, Cumbria, LA22 0LP, United Kingdom. tgp@ceh.ac.uk
Abstract:
In contrast to the relatively minor intra- and interspecies differences in blood cortisol levels reported for salmonid species, there is a more pronounced distinction between cortisol levels among the Salmonidae and the Cyprinidae, with both basal and stress-induced cortisol levels markedly higher in the latter. This study shows that in the chub, Leuciscus cephalus, a widely distributed European cyprinid, mean blood cortisol levels during stress (1500 ng mL(-1)) exceeded those reported for most other species of fish and, even in unstressed chub, cortisol levels (50-100 ng mL(-1)) were within the range known to cause immunosuppression, growth retardation, and reproductive dysfunction in salmonid fish. The chub appears to be atypical only with respect to plasma cortisol levels; the levels of plasma glucose and plasma lactate in unstressed and stressed chub are similar to those reported for other species. Plasma levels of 11-ketotestosterone in males and 17beta-estradiol in females are lower than those reported for salmonids but similar to those reported for other cyprinid species and display clear stress-induced reduction. Comparative analysis of the binding characteristics of the trout and chub gill cortisol receptor revealed that the total number of binding sites in gill tissue for each species was similar (B(max); approximately 50-100 fmol mg(-1) protein). However, the affinity of the binding site for cortisol displayed an eightfold difference between the species (rainbow trout: K(d) approximately 6 nM; chub: K(d) approximately 50 nM). Therefore, the potentially adverse effects of high circulating levels of cortisol found both at rest and under conditions of stress in chub may be offset by the lower affinity of the cortisol receptor, rather than the abundance of target-tissue receptor sites. This strategy is similar to that reported for some glucocorticoid-resistant rodents and New World primates.
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