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 17beta-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 Ca2+ 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 Ca2+ 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.