KeywordsCortisol Response Rejection Experience Human Evolutionary History Increase Blood Sugar Follow Stressor Exposure
Cortisol is a major steroid hormone in humans that is secreted by the adrenal cortex during the experience of stress as part of an adaptive coping response. Cortisol has wide-ranging effects, largely functioning to alter an organism’s immediate response to the stressor, modulate their response to a subsequent stressor, and aid in their adaptation to a chronic stressor.
Cortisol is synthesized and secreted by the adrenal cortex following stress-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis – the principal endocrine component of the stress response system. During the experience of stress, HPA axis activation causes a neuroendocrine cascade of events that result in the synthesis and secretion of glucocorticoids (GCs) – primarily cortisol in humans and corticosterone in other species. When environments or situations are judged to be harmful, threatening, or challenging (i.e., they are stressful), the central nervous system sends signals to the hypothalamus, which then secretes corticotropin-releasing hormone (CRH) to begin the neurobiological sequence of events that results in increased cortisol levels. CRH signals the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which is then taken up by receptors in the adrenal glands – a pair of relatively small endocrine glands laying above the kidneys. In turn, the adrenal cortex, which constitutes the outer covering of the adrenal gland, is stimulated to release cortisol.
As a corticosteroid and glucocorticoid, cortisol has diverse effects on physiological functioning, including: increasing blood pressure; increasing blood sugar levels; suppressing the immune system and reducing inflammation; promoting the breakdown of glycogen, lipids, and proteins; and generally, mobilizing the body’s energy resources. Compared to the relatively quick response of the sympathetic division of the autonomic nervous system during the experience of stress, the HPA axis mounts a more delayed, long-term response. However, the HPA system does have rapid effects as well, such as fast negative feedback into the HPA circuit, likely mediated by putative membrane steroid receptors (Nesse et al. 2010). Elevation of cortisol generally starts about 5 min following stressor exposure, with a peak between 10 and 30 min. Some of the effects of cortisol begin after an hour and may be observed for several hours or more. HPA activity is regulated by a hierarchy of feedback loops at different levels in the axis (see Gunnar and Vazquez 2006), and the sensitivity of these feedback loops is a major factor in determining HPA responsivity (Del Giudice et al. 2011).
As with any trait, the cortisol response is associated with cost-benefit trade-offs. While cortisol plays a role in regulating blood pressure, glucose metabolism, and immune function in order to facilitate acute biological responses to stressors, chronic secretion of glucocorticoids has been associated with various forms of pathology and disease. Chronic secretion of GCs has been linked to depression, insulin resistance and diabetes, hypertension and atherosclerosis, bone loss, and disorders involving decreased immune function (see McEwen 1998). Chronic GC secretion has also been shown to adversely affect the hippocampus – an area of the brain intimately linked to memory and learning – where decreased dendritic branching, loss of neurons, structural change in synaptic terminal, and neuron regeneration inhibition have been noted (see Sapolsky 1996). Despite the substantial costs that are sometimes linked to chronic GC secretion, natural selection has shaped this stress-responsive trait because the associated benefit to organisms is even more significant.
Functions of the Cortisol Response
Cortisol, and more broadly, glucocorticoids (GCs), modify an organism’s response to stress in several notable ways that vary as a function of environmental or situational context. In general, cortisol functions to mobilize available resources and serves as a counterbalance to sympathetic activation during the stress response process. Mobilization of resources may include those that are physiological or psychological in nature (see Sapolsky et al. 2000). Functioning as a counter-regulatory mechanism to help counterbalance the effects of sympathetic activation that can result in wear and tear on the body, cortisol can aid the recovery of the organisms as well (see Boyce and Ellis 2005).
What Does the HPA Axis Respond to?
Cortisol plays a pivotal role as mediator of environment adaptation, but significant physiological costs and side effects associated with elevated cortisol responses contribute to the HPA axis selectively responding to specific types of challenges. The HPA axis generally responds with increased cortisol when people (1) encounter unpredictable and/or uncontrollable challenges that require them to be alert and involve an element of anticipation, and (2) when challenges involve social-evaluation or relational threat (for review, see Dickerson and Kemeny 2004). The body of literature assessing HPA axis responses to stress overwhelmingly demonstrates that activation of the HPA axis and secretion of cortisol is strongly linked to social feedback. The HPA axis is highly responsive to separation and rejection experiences in family life for infants and children, while a similarly strong response is associated with older children in adults in the context of peer evaluation. Social evaluation was likely important in the context of evolutionary history, as negative evaluation carried with it the potential to incur a loss in social status or result in social ostracism, rejection, and loss of social bonds (Del Giudice et al. 2011).
Sex Differences in HPA Axis and Cortisol Response
Sex differences in biological and behavioral responses to stress likely developed during human evolutionary history. Although the basic architecture of the SRS – including the HPA axis – is the same for both sexes, the types of events or environmental contexts that trigger a response in men and women differ (Del Giudice et al. 2011). Generally, men tend to exhibit greater activation of the HPA axis than women during tasks related to achievement. The heightened response in males may be due to achievement-oriented tasks involving a challenge to status, subsequently enhancing the salience. Compared to males, females tend to demonstrate greater responsivity of the HPA axis in situations where social rejection is involved (Stroud et al. 2002). The enhanced salience of rejection experiences in females relative to males may be explained – in part – by Taylor et al. (2000) tend-and-befriend theory of biobehavioral responses to stress. Following this model of sex differences in behavioral and biological responses to stress, men follow a pattern of responsivity that closely follows the sympathetic fight-or-flight response. However, in females, environmental threats or challenges elicit a “tend-and-befriend” pattern of stress responding. This pattern involves caring for and protecting offspring as a tending response and also involves affiliation with a group and efforts to seek social support as a befriending response. Given the response preference in females for tending and befriending during times of stress, real or imagined rejection experiences would be expected to be highly salient for females, resulting in enhanced activation of the HPA axis and subsequent cortisol secretion.
Cortisol is a major steroid hormone in humans and end product of HPA system activation during the experience of stress, serving as a critical component of adaptive coping. Cortisol has a diverse range of behavioral and physiologic effects, functioning to alter an organism’s immediate response to a given stressor, modulate their response to a subsequent stressor, and facilitate adaptation to chronic stressors. Like all traits, the stress response associated with HPA system activation and increased cortisol is associated with cost-benefit trade-offs. The HPA axis is particularly responsive to unpredictable and/or uncontrollable challenges and social-evaluative threat. While the basic architecture of the HPA system is the same between sexes, differences in biological and behavioral responses to stress likely arose during human evolutionary history as a consequence of different environmental demands on males and females.
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