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Human Body Study

HPA Axis — Hypothalamic–Pituitary–Adrenal

The HPA axis The hypothalamus releases CRH, which stimulates the anterior pituitary to release ACTH, which stimulates the adrenal cortex to release cortisol. Cortisol exerts negative feedback on both the pituitary and the hypothalamus. Hypothalamus paraventricular nucleus Anterior pituitary corticotrophs Adrenal cortex zona fasciculata Target tissues ↑ blood glucose · ↓ inflammation ↑ vascular tone · circadian rhythm CRH (+ AVP) ACTH cortisol cortisol − − Solid arrows: stimulation. Dashed red: negative feedback.

Signaling chain

Section titled “Signaling chain”

CRH (hypothalamus, paraventricular nucleus) → ACTH (anterior pituitary corticotrophs) → cortisol (adrenal cortex, zona fasciculata). The hypothalamus also releases AVP, which synergizes with CRH to amplify ACTH output.

Function

Section titled “Function”

The body’s central stress-response and metabolic-regulation system. Cortisol mobilizes glucose (gluconeogenesis, insulin antagonism), suppresses inflammation and immune activity, supports vascular tone and blood pressure, and modulates mood and cognition. The axis also drives the circadian cortisol rhythm — peak shortly after waking, trough near midnight.

Feedback

Section titled “Feedback”

Negative feedback: cortisol suppresses both CRH and ACTH release at the hypothalamus and pituitary. This loop is the basis of the dexamethasone suppression test.

Clinical relevance

Section titled “Clinical relevance”
  • Excess — Cushing’s syndrome (central obesity, hypertension, hyperglycemia, skin thinning).
  • Deficiency — Addison’s disease / adrenal insufficiency (fatigue, hypotension, hyponatremia, hyperpigmentation if primary).
  • Chronic stress causes sustained activation, which can suppress the HPG and HPT axes.
  • Exogenous glucocorticoids suppress the axis and risk adrenal crisis on abrupt withdrawal.

Key labs

Section titled “Key labs”

Morning cortisol, ACTH, 24-hr urinary free cortisol, late-night salivary cortisol, dexamethasone suppression test, ACTH stimulation (cosyntropin) test.