© 2002 by The Society for Integrative and Comparative Biology
Is Stress More Than a Disease? A Comparative Look at the Adaptativeness of Stress1
1 Department of Biological Sciences, Texas Tech University, Box 4-3131, Lubbock, Texas 79409
2 Biology and Neuroscience, University of South Dakota, Vermillion, South Dakota 57069
Since the pioneering work of Hans Selye in the 1930s (Selye, 1936
, 1937) there has been a tremendous effort to understand how the nervous and endocrine systems coordinate the physiological response to stressors. Most work has focused on understanding the hypothalamic-pituitary-adrenal (HPA) axis and its role in stress. Within the last 20 yr scientists have purified and sequenced corticotropin-releasing hormone (CRH) and its receptors (Vale et al., 1981; DeSouza, 1995). Receptors for corticotropin and the glucocorticoid hormones have been cloned and mechanisms of action elucidated (Mountjoy et al., 1992; Bamberger et al., 1996). Significant progress has been made in defining afferent neuronal circuitry controlling the HPA axis during stress (Herman and Cullinan, 1997) and the link between stress and many major disease states has been clarified.
Although a good deal of Selye's original work addressed how organisms adapt to stressors (Selye, 1976), more recent studies have focused on disease-related aspects of stress. We are constantly bombarded, both in the scientific press and popular media, with reminders that stress is linked to feeding disorders, cancer, mental health, and reproductive and immune dysfunction as well as a host of other disorders. For a comparative biologist it is difficult to imagine that such a highly coordinated physiological response has evolved over millions of years simply to make animals sick. What are the adaptive features of stress? What are the evolutionary precursors of this response? Why has this response remained virtually unchanged in the vertebrate lineage? These are the questions that prompted the organization of this symposium.
It does not take an exhaustive review of the literature to realize that most of what we do know about stress and adaptation comes largely from studies on laboratory mammals that have never seen their natural environment. In recent years, increasing numbers of comparative endocrinologists have become interested in how animals living in their natural environment deal with stress. Four assumptions lie at the heart of this research:
- Examining the comparative endocrinology and evolution of stress can help identify common themes of neuroendocrine integration and control.
- Comparing widely used mammalian models with other vertebrates in laboratory or field settings makes it easier to recognize adaptations of behavior, reproductive strategy, and life history.
- Nonmammalian species are sometimes better models for unraveling complex neuroendocrine control mechanisms.
- Examining natural populations of animals can provide insight into adaptive features of stress previously unnoticed when studying laboratory mammals.
Our goal in organizing this symposium was to bring together a group of scientists working on diverse aspects of chemical signaling during stress in mammalian and nonmammalian organisms. We hoped to encourage an integrated approach to the topic by providing a forum for discussing the comparative neuroendocrinology of stress from molecular to behavioral levels. This issue includes twelve papers on a wide variety of topics, ranging from the phylogenetic diversity of the stress response to proximal and ultimate mechanisms of adaptation during stress. Greenberg et al. provide a historical overview of the stress response, pointing out some of the difficulties that arise when biologists define stress as a deleterious response that occurs when coping strategies fail. This is not to say that there are no clinical consequences to prolonged stress: Temporal patterns for detecting stressors and response integration are an underlying theme throughout all of the papers in this issue. However, given the clinical framework in which the concept of stress was developed (Selye was after all a clinician working on lab rats), it is important to broaden the concept to incorporate measurements of how real animals in their natural environments deal with challenges and perturbations. There is more at stake here than simply understanding how animals respond to stressors in the field. How will we ever begin to understand the role of stress in humans without understanding the evolutionary history of this response, i.e., how it came to be? Are we discussing evolutionary baggage, a vestigial response that was once important for dealing with life-threatening situations but is no longer needed? Or, are there aspects of stress responsiveness that are important for everyday well being that we simply overlook? It is presumptuous to assume that we can fully understand the role of stress solely by studying rodents and primates under lab conditions. Greenberg et al. also set the stage for the following papers in this issue by pointing out the importance of defining the cause and consequences of stress, focusing on the interpretation of stress-sensitive behaviors to illustrate their ideas.
Common themes of integration and regulation derive naturally from a comparative approach as is clearly illustrated in the next set of papers, which explore the phylogenetic diversity of the stress response. Stefano et al. discuss the evidence that peptides involved in the vertebrate stress response, including opioid peptides, are phylogentically ancient, and appear to play an important role in modulating immune function during stress in invertebrates. In mammals, opioid peptides act via receptors on lymphocytes to influence lymphocyte proliferation and cytokine production (McCarthy et al., 2001). Stefano et al. also discuss the contrasting roles of endogenous opioids and endogenous alkaloids, such as morphine, in directing immune cells to the site of an injury. Barton and Vijayan describe the classical endocrine response to stress, HPA or HPI cascade measured in fishes to humans, and set the stage for all following vertebrate taxa and discussions. They point out that among fishes, the magnitude and rate of response is dependent on the type and life history of the fish. Hayes (2001) presented evidence during the symposium that corticosterone from HPA activity stimulated by crowding stress during amphibian development might play an important role in regulating growth. Context dependent stress was a continuing theme during the symposium, reiterated by Greenberg, who describes socially dynamic changes in sympathetic and HPA response that modify body color and behavior, and by Wingfield and Kitaysky who describe plastic HPA responsivity dependent on an suite of environmental contextual information such as weather, habitat, body condition, social status, and life history stage.
The second group of papers deals with the proximal mechanisms of adaptation, focusing on the role of the HPA axis. In order for the adrenal glands to respond appropriately to perceived or real threats, their secretory activity must be coordinated with that of other effector systems. More importantly, since the adrenal glands have no way of detecting environmental changes on their own, they must rely on communication between hypothalamic CRH neurons and brain areas that perceive or detect a potential threat. Ziegler and Herman discuss the neurocircuitry controlling the HPA axis during stress. These authors approach the topic in an integrated way by not only providing an up to date review of afferent regulation of the HPA axis but also by examining the feedback mechanisms that limit the magnitude of the stress response. Bale et al. discuss their work using transgenic mice to elucidate the relative roles of the two CRH receptors in regulating the HPA axis and stress-sensitive behaviors such as feeding behavior. Different affinities for CRH and urocortin in combination with differential regional expression of CRH1-R and CRH2-R, may account not only for the diversity of behavioral and physiological effects elicited by CRH but also for temporal patterns of response, as suggested by recent studies on CRH control of feeding (reviewed by Cone, 2000).
One of the long-held beliefs associated with the view of stress as a disease is that many of the deleterious effects of stress are secondary to a decreased ability of the immune system to respond to a challenge. Dhabhar discusses the compelling evidence that just the opposite occurs when one considers that reductions in circulating leukocytes during stress actually represent a redistribution to the skin that aids in immune defense. Orchinik et al. (2001) described how a diverse variety of glucocorticoid receptor and binding proteins contributes to a variety of responses. They return to the theme of context specificity, adding that diverse behaviors mediated by differences in glucocorticoid receptor binding are also time and species specific. During the symposium, Moore (2001) pointed out that a rapid shift in behavioral state, for example from courtship to survival behavior, may be mediated by rapidly acting glucocorticoid membrane receptors. Finally, Glennemeier and Denver discuss the developmental sensitivity of CRH and the adrenal gland to a stressor in two amphibian species. The HPA axis plays a special developmental role in some anuran species, coordinating the timing of metamorphosis with unpredictable changes in the local environment such as pond drying (Denver, 1997).
Another component to comparative studies on stress focuses on how animals respond to ecologically relevant stressors in their natural environment. An important element of this research considers the role that stress plays in influencing social interactions, behavior, life history strategies and ultimately reproductive fitness and population stability in real animal populations (Wingfield et al., 1997). The last set of papers in this issue focuses on the role of stress and ultimate mechanisms of adaptation. Carruth et al. provide a fascinating look at the role of the HPA axis in home-stream migration of Pacific salmon. These authors postulate that elevated plasma cortisol during home-stream migration aids in recalling the imprinted memory of the home-stream chemical aroma. Carr discusses the hypothalamic control of feeding during stress, and examines the role of stress-related neuropeptides in redirecting behavior. In response to a threat, feeding behavior is usually suspended whereas behaviors required to deal with an imminent threat emerge. Stress-related neuropeptides, known for their anorexic effects in mammals, may have a primitive role in modulating the visuomotor circuitry involved in "feed or flee" sorts of decision making. During the symposium, Breuner and Hahn (2001) presented evidence that corticosterone acts as an endocrine mediator between the environment and behavior during inclement weather. Summers discusses the importance of examining temporal changes in stress-related hormones and neurotransmitters in interpreting stress effects on behavior. Flexibility of neuroendocrine response is an important aspect of adaptation to social context (Summers, 2001). Although Summers' work is focused on aggressive behavior in lizards, understanding temporal patterns in neurotransmitter release during aggressive behavior has wide implications, not only for other vertebrates (Winberg and Nilsson, 1993) but also invertebrates (Huber, 2001). Finally, Wingfield and Kitaysky point out that the response to labile perturbation factors (LPFs), including activation of the HPA axis, actually helps birds avoid the deleterious effects of stress. Their work raises the intriguing question of whether adrenal glucocorticoids are actually stress hormones or, in their words, "anti-stress" hormones. By looking at responses to LPFs, Wingfield and Kitaysky reiterate the importance of examining temporal patterns of detection, integration, and response.
In closing we would like to thanks all of the speakers and audience members for what turned out to be an exhausting but intellectually stimulating look into the adaptive features of stress. We would also like to thank Drs. John Pierce, Sunny Boyd, Martin Feder, and David Norris for logistical help in organizing the symposium. The symposium was made possible by funding from the NIMH (R13 MH62670), NSF (IBN 0100532), the Center for Biomedical Research Excellence (CoBRE, CHS) at the University of South Dakota on Neural Mechanisms of Adaptive Behavior, South Dakota EPSCoR, and the USD Office of Research.
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FOOTNOTES |
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1 From the Symposium: Stress—Is It More Than a Disease? A Comparative Look at Stress and Adaptation presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 3–7 January 2001, at Chicago, Illinois.
2 E-mail: jacarr{at}ttacs.ttu.edu
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