¶ HPA axis
Type: Neuroendocrine feedback axis
Components: Hypothalamus → Pituitary → Adrenal cortex
Hormones: CRH → ACTH → Cortisol
Regulation: Negative feedback via glucocorticoid receptors
Rhythm: Circadian — peak Cortisol in early morning
¶ Definition
The Hypothalamic-Pituitary-Adrenal axis is the primary neuroendocrine stress response system. It regulates Cortisol secretion through a cascade of CRH (corticotropin-releasing hormone) from the Hypothalamus, ACTH (adrenocorticotropic hormone) from the pituitary, and Cortisol from the adrenal cortex.
¶ The HPA Cascade
¶ Chronic activation → dysregulation
¶ Mechanism
Stress activates the paraventricular nucleus (PVN) of the Hypothalamus to release CRH. CRH stimulates anterior pituitary ACTH secretion. ACTH travels to adrenal cortex, stimulating Cortisol synthesis and release. Cortisol provides negative feedback to Hypothalamus and pituitary. The sympathetic nervous system acts in parallel. Chronic activation can lead to Cortisol resistance and dysregulation.
¶ Clinical Significance
HPA-axis dysfunction is central to chronic stress-related diseases, inflammation, metabolic disorders, and mental health conditions. Insulin resistance is a stronger predictor of HPA response than obesity alone. Both hyper- and hypo-cortisolism cause pathology, and Glucocorticoid Receptor sensitivity is as important as Cortisol levels.
¶ Key Facts
- Insulin resistance (IR) is a stronger predictor of HPA response than obesity in overweight individuals
- Chronic activation leads to Cortisol resistance in leukocytes
- Hypercortisolaemia without functional receptors causes neurotoxicity
- HPA axis shows circadian rhythm with peak Cortisol in morning
- Activated simultaneously with sympathetic nervous system during stress
- Dysregulation linked to Depression, Anxiety, PTSD, and metabolic syndrome
¶ Connections
- Hormones — Cortisol is primary stress hormone
- insulin resistance — IR predicts HPA responsiveness independent of obesity
- Hypercortisolaemia — excessive Cortisol output from chronic HPA activation
- Hypothalamus — paraventricular nucleus initiates HPA cascade via CRH release
- sympathetic nervous system — parallel activation during stress response
- metaflammation — HPA dysfunction contributes to chronic low-grade inflammation
- HPG Axis — stress-induced HPA activation suppresses reproductive axis
- HPT-axis — HPA-HPT crosstalk in metabolic regulation
¶ Module References
- Module 1
- Module 7