Estradiol increases glucagon's satiating potency in ovariectomized rats

Estradiol decreases meal size, food intake, and body weight in female rats. To investigate whether these effects of estradiol involve a change in the sensitivity of the signaling pathway through which pancreatic glucagon released during meals contributes to meal termination (satiation), glucagon or glucagon antibodies were infused via the hepatic portal vein in ovariectomized rats that were chronically treated with estradiol benzoate (2 microg/day sc) or vehicle alone (100 microl sesame oil). Infusions began at 1 h after dark onset, as rats were refed after 7 h of food deprivation. Glucagon (3 microg/min for 30 min) decreased feeding during the initial 45 min of food access in both groups of rats, but the inhibition was significantly greater in estradiol- than in oil-treated rats. Similarly, antagonism of endogenous glucagon by infusion of glucagon antibodies (a dose neutralizing 3 ng of glucagon in vitro during the first 3 min of refeeding) increased feeding significantly more in estradiol- than in oil-treated rats. These data indicate that an increase in the activity of the endogenous glucagon satiation-signaling pathway may be part of the mechanism for estradiol's inhibitory effect on feeding.