Sex difference in adrenergic receptor-mediated glycogenolysis in rat livers

Catecholamine-induced stimulation of hepatic glycogenolysis in male and female rats was studied by detecting the cytosolic free Ca2+ concentration ([Ca2+]i), cAMP generation and adrenergic receptor function. Increase in alpha 1-adrenergic receptor-mediated [Ca2+]i and beta-adrenergic receptor-mediated cAMP generation were examined using isolated hepatocytes. No difference was found in the alpha 1-adrenergic receptor-mediated response of [Ca2+]i in fura-2-loaded hepatocytes between males and females, while epinephrine-induced cAMP accumulation in hepatocytes was about 3-fold higher in females. The alpha 1- and beta-adrenergic receptor properties of the plasma membrane were evaluated by ligand binding studies using [3H]prazosin (alpha 1-adrenergic antagonist) and [125I]iodocyanopindolol (beta-adrenergic antagonist); and little sex difference was found in either affinity or the number of binding sites of [3H]prazosin and [125I]iodocyanopindolol. Activation of adenylate cyclase by forskolin and GTP-gamma-S was also similar for both sexes. These results suggest that the sex difference of beta-adrenergic response is due to a difference in the guanine nucleotide regulatory binding proteins (G proteins) and/or beta-adrenergic receptor-Gs protein (the stimulatory G protein of adenylate cyclase) coupling ability.