Epinephrine synthesis in the adrenal medulla requires the enzyme phenylethanolamine N-methyltransferase (PNMT), which methylates norepinephrine to epinephrine. Why is medullary PNMT activity dependent on the adjacent adrenal cortex?

• A Cortical chromaffin cells supply norepinephrine substrate directly to the medulla through gap junctions
• B High local concentrations of cortisol delivered by the corticomedullary portal venous system induce PNMT expression ✓
• C Aldosterone activates the tyrosine hydroxylase gene, increasing catecholamine synthesis
• D Cortisol inhibits COMT in the medulla, preventing degradation of norepinephrine before methylation

Explanation

Blood flows from the zona fasciculata and reticularis through an intra-adrenal portal system into the medulla, bathing chromaffin cells in cortisol concentrations far higher than systemic levels. Cortisol upregulates PNMT expression, which is why the adrenal medulla is the main site of epinephrine production and extra-adrenal chromaffin tissue secretes mostly norepinephrine. Option A is anatomically wrong since chromaffin cells are medullary, not cortical. Aldosterone has no role in catecholamine synthesis, eliminating C.

Reference: Ganong Review of Medical Physiology, 26th ed.

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