The brain-to-adrenal gland stress response system — the chain of command that produces cortisol when you’re under stress.CRH (hypothalamus) → ACTH (pituitary) → cortisol (adrenal cortex). Cortisol feeds back to suppress both CRH and ACTH production (negative feedback), creating the regulatory loop. Several peptides in the sleep and stress cluster interact with HPA axis components: CRH amplifies the stress response; NPY dampens it; cortisol’s circadian rhythm is the most prominent example of HPA axis cycling. Chronic HPA axis dysregulation is implicated in PTSD, major depression, and metabolic syndrome.