Is stress more than a disease? A comparative look at the adaptativeness of stress

Is Stress More Than a Disease? A Comparative Look at the Adaptativeness of Stress1

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 diseaserelated 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.