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Brian A Jackson


The present study has established that physiological concentrations of estradiol can modulate stress-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 sham-operated controls. In 17-estradiol (E2)-replaced OVEX rats, the hypoglycemia-induced rise in plasma EPI was significantly reduced compared to OVEX rats. This suppression was due to both decreased adrenal medullary output and increased clearance of EPI. Adrenal venous EPI concentration was significantly reduced in OVEX+E2 rats, suggesting that EPI secretion from the adrenalmedulla was decreased by E2 replacement. The underlying mechanism(s) of this apparent E2-mediated reduction in secretion could not be established since 1) the expression levels of the biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were not affected in OVEX+E2 rats, suggesting that EPI biosynthesis is similar in these and OVEX rats; and 2) agonist-induced increases in intracellular CaP2+P were identical in isolated adrenal medullary chromaffin cells exposed to E2 (10 nM) or vehicle for 48 hr, suggesting that stimulus secretion coupling is unaffected by E2 treatment. In contrast, plasma clearance of EPI was significantly increased in OVEX+E2 rats. Although 48 hr exposure to E2 had no effect on intracellular signaling in chromaffin cells, acute (3 min) exposure to micromolar concentrations of E2 dose-dependently and reversibly inhibited agonist-induced CaP 2+Ptransients. Consistent with this observation, acute (30 min) infusions of E2 also significantly reduced the insulin-induced increase in plasma EPI in OVEX rats. These data demonstrate that physiological levels of circulating E2 can modulate hypoglycemia-induced increases in plasma EPI. This effect appears to be mediated by the steroids influence on adrenal medullary EPI output and plasma EPI clearance; however the mechanism(s) underlying these E2-mediated modulations remain undetermined. This study has also established that acute exposure to supra-physiological levels of E2 can suppress hypoglycemia-induced increases in plasma EPI, due at least in part to inhibition of stimulus-secretion coupling.



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