Table 2.
Description and Age-Related Changes of Biomarkers of the HPA Axis
| Biomarkers of HPA axis | Brief definition | Function | Age-related changes | Association with disease |
| ACTH | Hormone released by anterior pituitary gland | Stimulates production of corticosteroids from adrenal cortex | Higher ACTH levels at nadir; reduced negative feedback | Elevations associated with disease states, including Addison’s and Cushing’s disease |
| CRH | Neuropeptide released by paraventricular nucleus of the hypothalamus | Initiates HPA axis response to stress; stimulates ACTH release from anterior pituitary | Increased activity in CRH but reduced CRH receptor binding in the pituitary | Elevations associated with depression and poor cognitive functioning |
| Cortisol | Corticosteroid released by zona fasciculata of adrenal cortex | Hormonal response to stress; mobilizes energy production, promotes glucogenesis, and conserves carbohydrates; reduces inflammation; feeds back to hypothalamus to reduce CRH release and dampen HPA axis activity | Higher cortisol levels at nadir; reduced negative feedback to hypothalamus | Persistently high levels associated with CHD, depression, anxiety, and poor cognitive functioning |
| AVP | Hormone released by the posterior pituitary gland | Acts centrally to support “fight-or-flight” response by stimulating ACTH release; also known as antidiuretic hormone; controls salt and water handling by kidney, thirst, and arterial blood pressure | Increased AVP release; reduced renal collecting duct sensitivity to AVP; loss of kidney AVP receptors; reduced AVP neuromodulation | Reduced urine concentrating abilities; poor blood pressure regulation; decreased cognitive functioning |
| DHEA-S/DHEA | Steroid produced by zona reticularis of adrenal cortex | Precursor of androgens; buffers the damaging effects of cortisol on the hippocampus and body | Declines | Lower levels related to CHD and poorer mental health |
Notes: ACTH = adrenocorticotropin hormone; AVP = arginine vasopressin; CHD = coronary heart disease; CRH = corticotropin-releasing hormone; DHEA-S = dehydroepiandrosterone-sulfate; DHEA = dehydroepiandrosterone; HPA = hypothalamic–pituitary–adrenal.