Corticosterone as a Physiological Biomarker: Decoding the Environment-Cort-Energy Paradigm

Glucocorticoid hormones (GCs) are widely used to assess physiological responses to environmental variation in wild animals, yet uncertainty remains over which circulating measures best reflect biologically meaningful stress responses. Total plasma GCs are most commonly measured across vertebrates. However, the fraction reaching tissues-the free hormone-is regulated by the plasma binding protein corticosteroid binding globulin (CBG). We examined corticosterone dynamics in a free-living songbird, the mountain white-crowned sparrow (Zonotrichia leucophrys oriantha), using 14 years of repeated physiological, morphological, and environmental measurements. We applied structural equation modeling to compare three conceptual frameworks describing plasma glucocorticoid physiology: models based on total circulating GCs, free GCs (unbound to CBG), and both total GCs with CBG variation. Across models, we identified links between environmental conditions, energetic state, and GC/CBG physiology, but the strength and structure of these relationships differed by sex and by the hormonal measure considered. Models examining relationships with free hormone included a greater number of supported explanatory variables than models based on total hormone alone, while models incorporating CBG dynamics provided additional explanatory structure and clarified sex-specific patterns not fully captured by either measure individually. Our results indicate that inferences about glucocorticoid-environment relationships depend strongly on how hormone physiology is characterized, highlighting the importance of integrating binding dynamics and sex-specific physiology when interpreting glucocorticoid variation.