Abstract
Clinical studies have demonstrated that estrogen replacement therapy suppresses stress‐induced increases in plasma catecholamines. The present study determined whether normal circulating levels of estrogen can modulate hypoglycemia‐induced increases in plasma epinephrine (EPI). In anesthetized female rats, insulin‐induced hypoglycemia (0.25 U/kg) increased plasma EPI concentration to a significantly greater extent in 14‐day ovariectomized (OVEX) rats compared to that in sham‐operated controls. In 17β‐estradiol (E2)‐replaced OVEX rats, the hypoglycemia‐induced rise in plasma EPI was reduced significantly when compared to that in vehicle‐replaced OVEX rats. OVEX and E2 replacement had no effect on tyrosine hydroxylase or phenylethanolamine N‐methyltransferase mRNA levels in the adrenal medulla. In isolated adrenal medullary chromaffin cells, agonist‐induced increases in intracellular Ca^2+^ were unaffected by 48‐hr exposure to 10 nM E2. In contrast, acute (3‐min) exposure to micromolar concentrations of E2 dose‐dependently and reversibly inhibited agonist‐induced Ca^2+^ transients. In addition, in OVEX rats, a constant infusion of E2 significantly reduced the insulin‐induced increase in plasma EPI concentration compared to that in vehicle‐infused controls. These data demonstrate that physiologic levels of circulating E2 can modulate hypoglycemia‐induced increases in plasma EPI. This effect seems independent of steroid influence on adrenal medullary secretion or biosynthesis. In contrast, acute exposure to high levels of E2 can also suppress hypoglycemia‐induced increases in plasma epinephrine, due at least in part to inhibition of stimulus‐secretion coupling. © 2004 Wiley‐Liss, Inc.