Glucocorticoid receptor expression as an integrative measure to assess glucocorticoid plasticity and efficiency in evolutionary endocrinology: A perspective.

Organisms have to cope with the changes that take place in their environment in order to keep their physical and psychological stability. In vertebrates, the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in mediating phenotypic adjustments to environmental changes, primarily by regulating glucocorticoids (GCs). Although circulating GCs have widely been used as proxy for individual health and fitness, our understanding of HPA regulation is still very limited, especially in free-living animals. Circulating GCs only exert their actions when they are bound to receptors, and therefore, GC receptors play a pivotal role mediating HPA regulation and GC downstream phenotypic changes. Because under challenging conditions GC actions (as well as negative feedback activation) occur mainly through binding to low-affinity glucocorticoid receptors (GR), we propose that GR activity, and in particular GR expression, may play a crucial role in GC regulation and dynamics, and be ultimately related to organismal capacity to appropriately respond to environmental changes. Thus, we suggest that GR expression will provide more comprehensive information of GC variation and function. To support this idea, we compile previous evidence demonstrating the fundamental role of GR on GC responses and the fine-tuning of circulating GCs. We also make predictions about the phenotypic differences in GC responsiveness - and ultimately HPA regulation capacity - associated with differences in GR expression, focusing on GC plasticity and efficiency. Finally, we discuss current priorities and limitations of integrating measures of GR expression into evolutionary endocrinology and ecology studies, and propose further research directions towards the use of GR expression and the study of the mechanisms regulating GR activity to gather information on coping strategies and stress resilience. Our goals are to provide an integrative perspective that will prompt reconsideration on the ecological and physiological interpretation of current GC measurements, and motivate further research on the role of GR in tuning individual responses to dynamic environments.