John C. Wingfield

The concept of allostasis in biology and biomedicine.

Living organisms have regular patterns and routines that involve obtaining food and carrying out life history stages such as breeding, migrating, molting, and hibernating. The acquisition, utilization, and storage of energy reserves (and other resources) are critical to lifetime reproductive success. There are also responses to predictable changes, e.g., seasonal, and unpredictable challenges, i.e., storms and natural disasters. Social organization in many populations provides advantages through cooperation in providing basic necessities and beneficial social support. But there are disadvantages owing to conflict in social hierarchies and competition for resources. Here we discuss the concept of allostasis, maintaining stability through change, as a fundamental process through which organisms actively adjust to both predictable and unpredictable events. Allostatic load refers to the cumulative cost to the body of allostasis, with allostatic overload being a state in which serious pathophysiology can occur. Using the balance between energy input and expenditure as the basis for applying the concept of allostasis, we propose two types of allostatic overload. Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in activation of the emergency life history stage. This serves to direct the animal away from normal life history stages into a survival mode that decreases allostatic load and regains positive energy balance. The normal life cycle can be resumed when the perturbation passes. Type 2 allostatic overload begins when there is sufficient or even excess energy consumption accompanied by social conflict and other types of social dysfunction. The latter is the case in human society and certain situations affecting animals in captivity. In all cases, secretion of glucocorticosteroids and activity of other mediators of allostasis such as the autonomic nervous system, CNS neurotransmitters, and inflammatory cytokines wax and wane with allostatic load. If allostatic load is chronically high, then pathologies develop. Type 2 allostatic overload does not trigger an escape response, and can only be counteracted through learning and changes in the social structure.

The "Challenge Hypothesis": Theoretical Implications for Patterns of Testosterone Secretion, Mating Systems, and Breeding Strategies

A combination of field and laboratory investigations has revealed that the temporal patterns of testosterone (T) levels in blood can vary markedly among populations and individuals, and even within individuals from one year to the next. Although T is known to regulate reproductive behavior (both sexual and aggressive) and thus could be expected to correlate with mating systems, it is clear that the absolute levels of T in blood are not always indicative of reproductive state. Rather, the pattern and amplitude of change in T levels are far more useful in making predictions about the hormonal basis of mating systems and breeding strategies. In these contexts we present a model that compares the amplitude of change in T level with the degree of parental care shown by individual males. On the basis of data collected from male birds breeding in natural or captive conditions, polygynous males appear less responsive to social environmental cues than are monogamous males. This model indicates that there may be widely different hormonal responses to male-male and male-female interactions and presumably equally plastic neural mechanisms for the transduction of these signals into endocrine secretions. Furthermore, evidence from other vertebrate taxa suggests strongly that the model is applicable to other classes

The Darwinian concept of stress: Benefits of allostasis and costs of allostatic load and the trade-offs in health and disease.

Why do we get the stress-related diseases we do? Why do some people have flare ups of autoimmune disease, whereas others suffer from melancholic depression during a stressful period in their life? In the present review possible explanations will be given by using different levels of analysis. First, we explain in evolutionary terms why different organisms adopt different behavioral strategies to cope with stress. It has become clear that natural selection maintains a balance of different traits preserving genes for high aggression (Hawks) and low aggression (Doves) within a population. The existence of these personality types (Hawks-Doves) is widespread in the animal kingdom, not only between males and females but also within the same gender across species. Second, proximate (causal) explanations are given for the different stress responses and how they work. Hawks and Doves differ in underlying physiology and these differences are associated with their respective behavioral strategies; for example, bold Hawks preferentially adopt the fight-flight response when establishing a new territory or defending an existing territory, while cautious Doves show the freeze-hide response to adapt to threats in their environment. Thus, adaptive processes that actively maintain stability through change (allostasis) depend on the personality type and the associated stress responses. Third, we describe how the expression of the various stress responses can result in specific benefits to the organism. Fourth, we discuss how the benefits of allostasis and the costs of adaptation (allostatic load) lead to different trade-offs in health and disease, thereby reinforcing a Darwinian concept of stress. Collectively, this provides some explanation of why individuals may differ in their vulnerability to different stress-related diseases and how this relates to the range of personality types, especially aggressive Hawks and non-aggressive Doves in a population. A conceptual framework is presented showing that Hawks, due to inefficient management of mediators of allostasis, are more likely to be violent, to develop impulse control disorders, hypertension, cardiac arrhythmias, sudden death, atypical depression, chronic fatigue states and inflammation. In contrast, Doves, due to the greater release of mediators of allostasis (surplus), are more susceptible to anxiety disorders, metabolic syndromes, melancholic depression, psychotic states and infection.

Reproduction and resistance to stress: when and how.

Environmental and social stresses have deleterious effects on reproductive function in vertebrates. Global climate change, human disturbance and endocrine disruption from pollutants are increasingly likely to pose additional stresses that could have a major impact on human society. Nonetheless, some populations of vertebrates (from fish to mammals) are able to temporarily resist environmental and social stresses, and breed successfully. A classical trade‐off of reproductive success for potential survival is involved. We define five examples. (i) Aged individuals with minimal future reproductive success that should attempt to breed despite potential acute stressors. (ii) Seasonal breeders when time for actual breeding is so short that acute stress should be resisted in favour of reproductive success. (iii) If both members of a breeding pair provide parental care, then loss of a mate should be compensated for by the remaining individual. (iv) Semelparous species in which there is only one breeding period followed by programmed death. (v) Species where, because of the transience of dominance status in a social group, individuals may only have a short window of opportunity for mating. We suggest four mechanisms underlying resistance of the gonadal axis to stress. (i) Blockade at the central nervous system level, i.e. an individual no longer perceives the perturbation as stressful. (ii) Blockade at the level of the hypothalamic‐pituitary‐adrenal axis (i.e. failure to increase secretion of glucocorticosteroids). (iii) Blockade at the level of the hypothalamic‐pituitary‐gonad axis (i.e. resistance of the reproductive system to the actions of glucocorticosteroids). (iv) Compensatory stimulation of the gonadal axis to counteract inhibitory glucocorticosteroid actions. Although these mechanisms are likely genetically determined, their expression may depend upon a complex interaction with environmental factors. Future research will provide valuable information on the biology of stress and how organisms cope. Such mechanisms would be particularly insightful as the spectre of global change continues to unfold.

Do baseline glucocorticoids predict fitness

Baseline glucocorticoid (cort) levels are increasingly employed as physiological indices of the relative condition or health of individuals and populations. Often, high cort levels are assumed to indicate an individual or population in poor condition and with low relative fitness (the Cort-Fitness Hypothesis). We review empirical support for this assumption, and find that variation in levels of baseline cort is positively, negatively, or non-significantly related to estimates of fitness. These relationships between levels of baseline cort and fitness can vary within populations and can even shift within individuals at different times in their life history. Overall, baseline cort can predict the relative fitness of individuals and populations, but the relationship is not always consistent or present.

Allostasis and Allostatic Load

Allostasis and allostatic load are terms which supplement the classic terms homeostasis and stress. Allostasis is the active process that leads to adaptation to a stressor, and mediators of allostasis include stress hormones as well as the autonomic nervous systems and pro-inflammatory cytokines and metabolic hormones. Allostatic load and its more severe form, allostatic overload, represent the cumulative effects of chronic physiologic stress, which may be generated by internal processes (e.g., anxiety) and by external factors such as chronic stressors or by life styles (e.g., overeating, insufficient sleep) that also dysregulate the mediators of allostasis. Consequences of allostatic overload include many of the common diseases of modern life. In nature, however, allostatic load is used to achieve beneficial effects such as putting on fat for hibernation.

Avoiding the ‘Costs’ of Testosterone: Ecological Bases of Hormone-Behavior Interactions

A combination of laboratory and field investigations of birds has shown that expression of behavior such as territorial aggression can occur throughout the year in many species and in different life history stages. Although it is well known that testosterone regulates territorial aggression in males during the breeding season, the correlation of plasma testosterone and aggression appears to be limited to periods of social instability when a male is challenged for his territory by another male, or when mate-guarding a sexually receptive female. How essentially identical aggression is modulated in non-breeding life history stages is not fully resolved, but despite low circulating levels of testosterone outside the breeding season, expression of territorial aggression does appear to be dependent upon aromatization of testosterone and an estrogen receptor-mediated mechanism. There is accumulating evidence that prolonged high levels of circulating testosterone may incur costs that may potentially reduce lifetime fitness. These include interference with paternal care, exposure to predators, increased risk of injury, loss of fat stores and possibly impaired immune system function and oncogenic effects. We propose six hypotheses to explain how these costs of high testosterone levels in blood may be avoided. These hypotheses are testable and may reveal many mechanisms resulting from selection to avoid the costs of testosterone. It should also be noted that the hypotheses are applicable to vertebrates in general, and may also be relevant for other hormones that have a highly specialized suite of actions in one life history stage (such as breeding), but also have a limited action in other life history stages when the full spectrum of effects would be inappropriate.

Interactions of corticosterone with feeding, activity and metabolism in passerine birds

Corticosterone (B) may play a direct role in the promotion of feeding behavior under conditions of nutritional stress. However, effects of exogenous B and nutritional stress in passerines indicate a complex relationship of fed state, perceived or anticipated nutritional stress, and previous history. In a series of investigations on caged White-crowned Zonotrichia leucophrys and Song Sparrows Z. melodia, foraging behaviors and feeding rates were unaffected by exogenous B in fed birds. When food was returned, birds implanted with B refed for longer and with greater intensity following the 24 hour fast. Additionally, B-implanted birds showed lower activity (perch hopping) than controls when fed ad libitum, but when fasted this trend reversed with B-implanted birds showing increased activity and apparent escape behavior. In a second study, small flocks of Pine Siskins Carduelis pinus and Darkeyed Juncos Junco hyemalis held in aviaries and fasted for 24 hours had higher plasma levels of B than similar flocks that had been allowed to refeed for 1 hour after fasting. However, the highest levels of B in fasted birds were still lower than in free-living conspecifics exposed to capture stress. This low amplitude modulation of plasma B levels in relation to fed state was corroborated by results from free-living Pine Siskins and Lapland Longspurs Calcarius lapponicus captured during snow storms. In spite of unusually high feeding intensities during the storm, individuals of only some Pine Siskins and no Lapland Longspurs had elevated circulating levels of B. In the latter species, serial samples revealed very high levels of B within 15 minutes of capture suggesting enhanced adrenal secretory activity as a result of the storm. Finally, in White-crowned Sparrows, exogenous B substantially reduced overnight metabolic expenditure by reducing the frequency and amplitude of arousal bouts during the night. This suggested a possible energy savings effect of B during the hours when foraging was impossible and, possibly, insurance that the individual will retain sufficient resources to seek food the following day. Taken together, our data suggest that B may be important for initiation of food-searching during periods of food deprivation. Only small increases in B secretion appear to be required thus facilitating a rapid return to homeostasis after food is located. Although under prolonged nutritional stress the basal levels of B remained low, adrenal potential to secrete B in response to further stress increased dramatically.

Allostatic load, social status and stress hormones: the costs of social status matter

Cooperation and social support are the major advantages of living in social groups. However, there are also disadvantages arising from social conflict and competition. Social conflicts may increase allostatic load, which is reflected in increased concentrations of glucocorticoids. We applied the emerging concept of allostasis to investigate the relation between social status and glucocorticoid concentrations. Animals in a society experience different levels of allostatic load and these differences may predict relative glucocorticoid concentrations of dominant and subordinate individuals. We reviewed the available data from free-ranging animals and generated, for each sex separately, phylogenetic independent contrasts of allostatic load and relative glucocorticoid concentrations. Our results suggest that the relative allostatic load of social status predicts whether dominants or subordinates express higher or lower concentrations of glucocorticoids. There was a significant correlation between allostatic load of dominance and relative glucocorticoid concentrations in both females and males. When allostatic load was higher in dominants than in subordinates, dominants expressed higher levels of glucocorticoids; when allostatic load was similar in dominants and subordinates, there were only minor differences in glucocorticoid concentrations; and when allostatic load was lower in dominants than in subordinates, subordinates expressed higher levels of glucocorticoids than dominants. To our knowledge, this is the first model that consistently explains rank differences in glucocorticoid concentrations of different species and sexes. The heuristic concept of allostasis thus provides a testable framework for future studies of how social status is reflected in glucocorticoid concentrations.

Effects of Experimental Manipulation of Testosterone Levels on Parental Investment and Breeding Success in Male House Sparrows

-Breeding male House Sparrows (Passer domesticus) were implanted with testosterone (T), the antiandrogen flutamide (F), or an empty capsule as a control (C). Parental feeding rates by C-treated males were high until nestlings reached 10 days of age, then declined significantly. This is the typical temporal pattern of parental behavior for free-living males. In contrast, F-treated males fed young at a high rate throughout the nestling stage, while T-treated males fed young much less frequently and were more involved in male-male competition during this period of time. There was a significant decrease in the breeding success of T-treated males resulting from increased starvation of their nestlings. Despite lowered levels of testosterone, F-treated males were able to maintain control of their nest boxes and exhibited normal sexual behavior. During the subsequent brood, breeding success of T-treated males again was reduced by nestling starvation. Our results demonstrate that high levels of testosterone inhibit the expression of parental care in male House Sparrows. Moreover, they suggest that the typical pattern of testosterone levels in males (high when mate guarding and low when feeding young) represents an optimal compromise between allocation of effort to male-male competition vs. parental care. Received 10 July 1986, accepted 1 March 1987. CORRELATIONAL and experimental studies on House Sparrows (Passer domesticus) have suggested that the activities of breeding males represent a trade-off between investment in malemale competition vs. parental care. In males, circulating levels of testosterone reflect this trade-off, being elevated when male-male competition is high and low when parental investment is high. We have suggested that this pattern maximizes an individuals overall reproductive output, even if it results occasionally in a reduction of fecundity (Hegner and Wingfield 1986a, 1987). In this study, we tested experimentally whether the variable pattern of male investment represents an optimization by artificially altering that pattern. This was achieved by altering the endocrine and behavioral state of males with subcutaneous hormone implants. We tested specifically whether elevated levels of testosterone during the last portion of the nestling stage, the interbrood interval, and the egglaying stage are critical for (1) defense of the I Present address: Department of Zoology, NJ-15, University of Washington, Seattle, Washington 98195 USA. nesting site, (2) normal sexual behavior, and (3) successful mate guarding. We also tested (4) whether lowered levels of testosterone during incubation and the early portion of the nestling stage are necessary for the expression of parental care.