Epinephrine synthesis in the adrenal medulla requires phenylethanolamine-N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. Why does bilateral adrenalectomy without glucocorticoid replacement reduce epinephrine production even if chromaffin tissue persists elsewhere?

• A Cortisol delivered through the corticomedullary portal system induces PNMT ✓
• B ACTH directly induces PNMT gene expression in extra-adrenal chromaffin cells
• C Norepinephrine uptake into chromaffin granules requires aldosterone
• D Tyrosine hydroxylase activity falls without adrenal cortical support

Explanation

Venous blood draining the zona fasciculata carries very high cortisol concentrations through the corticomedullary portal vessels to the chromaffin cells, where cortisol induces PNMT expression. Without glucocorticoid replacement, PNMT induction is lost and norepinephrine cannot be methylated efficiently. Tyrosine hydroxylase, the rate-limiting step for catecholamine synthesis itself, is regulated by sympathetic nerve activity rather than cortisol, killing option D.

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

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