Monday, April 7, 2008

HPA Axis, neuroendocrine factors, and stress

Tsigos, C. & Chrousos, G.P. (2002). Hypothalamic-pituitary-adrenal axis, neuroendocrine factors, and stress. Journal of Psychosomatic Research, 53, 865-871.

Psychology is concerned with the transactions and interactions we have with the world. Stress research examines how we respond to transactions that are stressful. This paper does a great job to illustrate the complexity of our physiological responses to stressors.

CRH/AVP. The paper begins with our physiological response following detection of a stressor. CRH and AVP are secreted into a special portal system and activate neurons of the paraventricular nuclei (PVN) of the hypothalamus, which primarily kicks off activation of the greater hypothalamic-pituitary-adrenal (HPA) axis.

LC/NE system. The locus ceruleus and other noradrenergic cell groups of the medulla and pons, collectively known as the LC/NE system, serve as a global alarm system, using brain epinephrine to execute autonomic and neuroendocrine responses.

The autonomic axis. The ANS provides rapid response to stress, engaging the SNS and withdrawing the PSNS, and enacting cardiovascular, respiratory, gastrointestinal, renal, and endocrine changes.

The HPA Axis. CRH and AVP normally follow certain circadian rhythms, with increasing pulses seen in the early morning hours and decreasing throughout the day. During acute stress, pulsations in this portal system markedly increase, resulting in release of ACTH from the pituitary into the general bloodstream, which finally results in secretion of cortisol and other glucocorticoids from the adrenal cortex. These corticoids involve the whole body in the organism's response to stress and ultimately contribute to the termination of the response via inhibitory feedback.

Other changes. Concomitant with the aforementioned changes, the sympathetic-adrenomedullary system (SAM) influences the body organs, and vagal and sacral parasympathetic responses are also instantiated mediating our gut responses to stress.

The paper also goes into advanced topics including interactions that exist between the HPA axis and the immune system, interactions between the HPA and the gonadal and growth axes, and interactions between the HPA and metabolism. It also discusses pathologies related to the HPA axis. A spectrum of conditions may be associated with increased and prolonged activation of the HPA axis, including melancholic depression, anorexia nervosa, OCD, panic anxiety, excessive exercising, and childhood sexual abuse. Another group of conditions may be associated with hypoactivation of the stress system, including atypical depression, seasonal depression, and chronic fatigue syndrome. Antalarmin, a CRH-R1 antagonist, was also mentioned as being a potentially important drug to combat HPA axis disorders characterized by HPA and LC/NE hyperactivity in the future.

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