Beyond circulating hormones: Investigations upstream and downstream of plasma corticosterone

The hypothalamus-pituitary-adrenal (HPA) axis secretes the glucocorticoid hormones cortisol and corticosterone (CORT), which are important mediators of the stress response. The HPA axis has been a major focus of research by physiological ecologists for the last 50 years, and this work has elucidated many aspects of CORT's function in free-living animals. However, there are still important outstanding questions that have not been answered using the traditional approach of examining changes in circulating hormone titers in response to different stimuli. These include the questions of why CORT shows predictable seasonal patterns across many vertebrate species, and what HPA changes we should expect to see in chronically-stressed animals. In this dissertation, I examined broader HPA functioning by quantifying not just baseline and stress-induced plasma CORT, but also assessing physiological measures both "upstream" and "downstream" of CORT titers in house sparrows (Passer domesticus). These included quantifying an animal's maximal capacity to secrete CORT, its ability to shut down CORT via negative feedback, and, the main focus of this dissertation, receptor density in various target tissues, which reveals an animal's responsiveness to circulating hormone. My overall hypothesis was that adrenal sensitivity, negative feedback and CORT receptor concentrations would be modulated independently from plasma CORT titers, in ways that would clarify our understanding of HPA function in wild animals.;As hypothesized, different components of the HPA axis did vary independently, and in many cases, my findings shed light on the results of past studies only examining hormone titers. For example, I found that CORT receptors in pectoralis, but not gastrocnemius muscle increased with chronic stress. This suggests a potential mechanism for the specific wasting of pectoralis muscle seen with exogenous CORT administration in previous bird studies. These studies also reveal several new avenues for future research - for example, patterns in receptor density in different metabolic tissues suggest that in response to stressors, sparrows mobilize different tissues for energy at different times of year. Overall, the fact that different components of the HPA axis may be regulated somewhat independently emphasizes the importance of examining factors other than plasma CORT titers in understanding CORT's actions.