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The Hypothalamic-Pituitary-Adrenal Axis: The Actions of the Central Nervous System and Potential Biomarkers

Kelly L. Olson, Ph.D.;David T. Marc, M.S.; Lindsay A. Grude, B.S.; Corena J. McManus, M.S.; Gottfried H. Kellermann, Ph.D.

The adrenal glands are part of an adaptive system involved in the maintenance of a homeostatic biological balance in response to stress. The adrenal glands release cortisol, epinephrine, and norepinephrine to preserve a healthy, but dynamic equilibrium. Specific brain nuclei control adrenal gland function either through the actions of the hypothalamic-pituitary-adrenal (HPA) axis, initiated by traditional HPA drivers like corticotrophin releasing factor (CRF) from the hypothalamus, or through direct innervation by stimulated preganglionic sympathetic nerves. These pathways can be activated by physical or emotional stressors as well as inflammatory processes which can activate adrenal activity through the signaling of various cytokines. The continuum of hyperstimulation of the HPA axis from an acute insult to a chronic saturation of the system is led by varying degrees of adrenal collapse eventually giving way to adrenal fatigue. The functionality of the HPA axis can be evaluated with peripheral biomarkers such as urinary epinephrine and norepinephrine and salivary cortisol. These HPA biomarkers help practitioners identify contributing factors to various clinical conditions and provide insight into potential intervention points. By understanding the pathways that can lead to altered HPA axis activity and by using biomarkers to assess HPA functionality, health care practitioners can make more informed clinical decisions to enhance patient care.

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