The adrenal medulla releases epinephrine and norepinephrine in response to sympathetic nervous system activation (chromaffin cells lack extensive synaptic input and respond directly to acetylcholine), triggering the fight-or-flight response through effects on heart rate, blood pressure, and metabolism. These catecholamines bind adrenergic receptors and are rapidly metabolized by monoamine oxidase and catechol-O-methyltransferase.
From your study of the endocrine system, you know that hormones are chemical messengers released into the bloodstream to act on distant target cells. From the autonomic nervous system, you know that the sympathetic division prepares the body for action. The adrenal medulla sits at the intersection of these two systems — it is neural tissue that functions as an endocrine gland, releasing hormones directly into the blood in response to nervous system commands.
The adrenal medulla is composed of chromaffin cells, which are embryologically derived from the same neural crest tissue that produces sympathetic postganglionic neurons. Unlike typical postganglionic neurons that release norepinephrine at a specific target organ, chromaffin cells release their catecholamines into the bloodstream, where they reach every tissue in the body simultaneously. This is the key distinction: sympathetic nerve fibers produce rapid, localized responses (your heart rate increases within a beat), while adrenal medullary secretion produces a slower but body-wide hormonal wave. The medulla is innervated by sympathetic preganglionic fibers that release acetylcholine, which binds nicotinic receptors on chromaffin cells and triggers catecholamine exocytosis.
The two main catecholamines released are epinephrine (about 80% of secretion) and norepinephrine (about 20%). Epinephrine is synthesized from norepinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT), which is induced by cortisol flowing directly from the adrenal cortex through a portal blood supply — an elegant anatomical arrangement where the cortex literally bathes the medulla in the hormone needed to produce epinephrine. Once released, these catecholamines bind to adrenergic receptors (alpha and beta subtypes) on target cells, producing the classic fight-or-flight effects: increased heart rate and contractility (beta-1), bronchodilation (beta-2), vasoconstriction in skin and gut (alpha-1), and mobilization of glucose from liver glycogen (beta-2).
The effects of circulating catecholamines are powerful but short-lived. Enzymes called monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) rapidly degrade epinephrine and norepinephrine, with a plasma half-life of only one to two minutes. This rapid clearance ensures that the fight-or-flight response does not persist indefinitely — once the threat passes and sympathetic stimulation subsides, catecholamine levels drop quickly and the body returns toward baseline. Clinically, measuring catecholamine metabolites (metanephrines and vanillylmandelic acid) in urine is used to diagnose catecholamine-secreting tumors such as pheochromocytoma, where unregulated secretion causes dangerous episodic hypertension.