HPA flexibility and FKBP5 : promising physiological targets for conservation

Abstract

Hypothalamic–pituitary–adrenal axis (HPA) flexibility is an emerging concept recognizing that individuals that will cope best with stressors will probably be those using their hormones in the most adaptive way. The HPA flexibility concept considers glucocorticoids as molecules that convey information about the environment from the brain to the body so that the organismal phenotype comes to complement prevailing conditions. In this context, FKBP5 protein appears to set the extent to which circulating glucocorticoid concentrations can vary within and across stressors. Thus, FKBP5 expression, and the HPA flexibility it causes, seem to represent an individual's ability to regulate its hormones to orchestrate organismal responses to stressors. As FKBP5 expression can also be easily measured in blood, it could be a worthy target of conservation-oriented research attention. We first review the known and likely roles of HPA flexibility and FKBP5 in wildlife. We then describe putative genetic, environmental and epigenetic causes of variation in HPA flexibility and FKBP5 expression among and within individuals. Finally, we hypothesize how HPA flexibility and FKBP5 expression should affect organismal fitness and hence population viability in response to human-induced rapid environmental changes, particularly urbanization. This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.

Endocrine responses to environmental variation

“…Interestingly, variability in receptor density between individuals masked the correspondence between plasma glucocorticoid levels and physiological responses [ 26 ], indicating that plasma levels alone may be an insufficient indicator of stress responses. Ultimately, the crucial aspect of glucocorticoid signalling is its capacity to respond to and compensate for sudden changes in the environment [ 27 ], and this capacity is not necessarily reflected in isolated measures of circulating hormone levels. An alternative to measuring circulating hormone levels is the measurement of FKBP5, a protein in the glucocorticoid receptor complex that regulates receptor function and activity.…”

“…An alternative to measuring circulating hormone levels is the measurement of FKBP5, a protein in the glucocorticoid receptor complex that regulates receptor function and activity. FKBP5 sets the scope of glucocorticoid responses to environmental stressors [ 27 ]. Monitoring FKBP5 may therefore be a more effective way to assess endocrine flexibility and the efficacy of the physiological stress responses in individuals [ 27 ].…”

“…FKBP5 sets the scope of glucocorticoid responses to environmental stressors [ 27 ]. Monitoring FKBP5 may therefore be a more effective way to assess endocrine flexibility and the efficacy of the physiological stress responses in individuals [ 27 ].…”

“…Endocrine flexibility considers hormones as information carriers, which are deployed to effect within-individual rapid and reversible changes in physiological regulation in response to unpredictable challenges [ 4 , 32 ]. Useful information is contained in context-dependent changes in hormone concentrations coupled with receptor binding sensitivities, and individuals that can obtain the ‘best’ information about stressors will also be capable of mounting the most effective response [ 4 , 27 ].…”