Cyclic estradiol replacement increases the satiety effect of CCK-8 in ovariectomized rats

The influence of cyclic ovarian hormone replacement therapy on the satiety effect of exogenous CCK-8 was determined to investigate the mechanism mediating the preestrous decrease in meal size in female rats. Once weekly, food-deprived ovariectomized rats were IP injected with 0.5-4 micrograms/kg CCK-8 and offered 0.4-0.8 M sucrose 52 h after the second of two daily SC injections of 2.5 or 10 micrograms estradiol benzoate or vehicle and 4 h after 500 mg progesterone or vehicle. In each of three tests, estradiol significantly increased CCK-8's inhibitory effect on sucrose intake. In contrast, progesterone alone or in combination with estradiol did not consistently influence the satiating potency of CCK-8. The interaction of estradiol and CCK-8 was clearest for the dose of 4 micrograms/kg CCK-8. The interaction occurred during diurnal tests and during dark-onset tests in which estradiol did not decrease baseline sucrose intake. These results demonstrate that a cyclic regimen of estradiol replacement in ovariectomized rats is sufficient to enhance the satiating effect of exogenous CCK-8 and that simultaneous progesterone treatment does not influence this effect. Potentiation of the satiating effect of CCK released from the small intestine by ingested food may be one of the mechanisms by which food intake decreases during the period of high estrogen concentration in the estrus cycle.