Integrating theoretical and empirical approaches for a robust understanding of endocrine flexibility.

There is growing interest in studying hormones beyond single 'snapshot' measurements, as recognition that individual variation in the endocrine response to environmental change may underlie many rapid, coordinated phenotypic changes. Repeated measures of hormone levels in individuals provide additional insight into individual variation in endocrine flexibility - that is, how individuals modulate hormone levels in response to the environment. The ability to quickly and appropriately modify phenotype is predicted to be favored by selection, especially in unpredictable environments. The need for repeated samples from individuals can make empirical studies of endocrine flexibility logistically challenging, but methods based in mathematical modeling can provide insights that circumvent these challenges. Our Review introduces and defines endocrine flexibility, reviews existing studies, makes suggestions for future empirical work, and recommends mathematical modeling approaches to complement empirical work and significantly advance our understanding. Mathematical modeling is not yet widely employed in endocrinology, but can be used to identify innovative areas for future research and generate novel predictions for empirical testing.

Mathematical modeling reveals how the speed of endocrine regulation should affect baseline and stress-induced glucocorticoid levels.

Unpredictable environmental changes displace individuals from homeostasis and elicit a stress response. In vertebrates, the stress response is mediated mainly by glucocorticoids (GCs) which initiate physiological changes while minimizing allostatic overload. Individuals and species vary consistently in baseline and stress-induced GC levels and the speed with which GC levels can be upregulated or downregulated, but the extent to which variation in hormone regulation influences baseline and stress-induced GC levels is unclear. Using mathematical modeling, we tested how GC regulation rate, frequencies and durations of acute stressors, fitness functions, and allostatic overload affect GC levels during control and acute stress periods. As GC regulation rate slows, baseline and acute stress-induced GC levels become more similar. When the speed of up- and downregulation decreased, hormone levels became more linked to anticipated future conditions to avoid fitness costs of mismatching a new environmental state. More frequent acute stressors caused baseline and acute stress-induced GC levels to converge. When fitness was more tightly linked to hormone levels during acute stress periods than during control states, the speed of upregulation influenced optimal hormone levels more than the downregulation rate. With allostatic overload costs included, predicted GC levels were lower and more dependent on the frequency of past acute stressors. Our results show the value of optimality modeling to study the hormonal response to stressors and suggest GC levels depend on past and anticipated future environmental states as well as individual differences in hormone regulation.

Pre-GnRH and GnRH-induced testosterone levels do not vary across behavioral contexts: A role for individual variation.

Hormones can facilitate the expression of behavior, but relatively few studies have considered individual variation and repeatability in hormone-behavior relationships. Repeated measures of hormones are valuable because repeatability in hormone levels might be a mechanism that drives repeatability in behavior ("personality"). Testosterone is predicted to promote territorial aggression and suppress parental behaviors. In our population of eastern bluebirds (Sialia sialis), parental care and nest defense aggression toward a heterospecific are repeatable. We tested the hypothesis that repeatability of testosterone levels within individuals underlies repeatable behaviors observed in our population. We measured nestling provisioning and aggressive nest defense against a heterospecific. After behavioral observations we captured either the male or female bluebird, and determined initial testosterone levels and maximum capacity of the gonads to secrete testosterone by injecting gonadotropin-releasing hormone (GnRH). We found among-individual variation in initial testosterone levels for males and females. Individual males were repeatable in both initial and GnRH-induced testosterone levels across behavioral contexts, while individual females were repeatable in GnRH-induced testosterone levels. However, testosterone levels were not significantly related to parental or nest defense behaviors, suggesting that repeatable testosterone levels may not drive repeatable parental and heterospecific nest defense behaviors in this population. The absence of a relationship between testosterone and parental and heterospecific nest defense behaviors might be due to among-individual variation in testosterone levels. Considering the sources of variation in testosterone levels may reveal why some populations exhibit high individual variation in hormone levels.