CRH

CRH is the hypothalamus's first move in the body's stress response. When you face danger, illness, or even an early-morning wake-up, CRH is released to the anterior pituitary and tells it to secrete ACTH, which then prompts the adrenal glands to pour out cortisol.

It is a peptide hormone made by neurons in the paraventricular nucleus of the hypothalamus and delivered through the portal system. CRH sits at the very top of the hypothalamic-pituitary-adrenal axis — the central pathway by which the brain converts a perceived stressor into a hormonal, whole-body response.

CRH secretion follows a daily rhythm, peaking in the early morning hours, which is why cortisol is highest just before we wake. On top of this baseline rhythm, acute stress can sharply boost CRH and rapidly raise cortisol to mobilize energy and dampen inflammation.

The system is reined in by negative feedback: cortisol suppresses both CRH and ACTH. This is the basis of the dexamethasone suppression test, in which a synthetic glucocorticoid is given to see whether the axis can be switched off normally — a key tool in diagnosing Cushing's syndrome.