Decreased cAMP responsiveness to glucagon in livers from ethynyl estradiol treated rats.

The effects of glucagon on the concentration and output of cAMP were studied in liver slices and in perfused livers from female rats and from animals treated with ethynyl estradiol (15 μg/kg daily for 14 days). The basal content of cAMP in liver slices, or of cAMP released into the perfusion medium in the absence of glucagon, was unaffected by prior treatment of the animal with estrogen. When glucagon was added to the medium, the concentration of cAMP in liver slices was 2.29 ± 0.32 and 1.10 ± 0.11 pmol cAMP/mg wet weight from control and ethynyl estradiol treated rats, respectively. When glucagon was added, the output of cAMP by perfused livers was maximal at 20 minutes with livers from either control or ethynyl estradiol treated rats. Output of cAMP by the perfused liver, when glucagon was added to the medium, was 8.76 ± 0.69 and 1.84 ± 0.08 nmol/g by livers from control and ethynyl estradiol treated rats, respectively. This effect was the same whether animals had been fasted for 12 hours previously, or were allowed free access to food until sacrifice. Clearly, as measured by cAMP accumulation, prior treatment of the rat with ethynyl estradiol reduced the sensitivity of the hepatic cAMP response to glucagon.