Cyclic estradiol treatment modulates the orexigenic effects of ghrelin in ovariectomized rats

Data from a wide variety of mammalian species indicate that feeding behavior can be influenced by changes in endogenous estrogens and exogenous estrogenic treatments. Ghrelin is an important physiological signal for the regulation of energy balance, and ghrelin treatment increases eating and body weight in male rodents. The following studies evaluated the hypothesis that the inhibitory effects of estradiol on feeding involve interactions with orexigenic peptides by examining the ability of estradiol to modulate the behavioral effects of ghrelin in female rats. In these experiments, adult rats were ovariectomized and assigned to an estradiol benzoate (EB) or an oil (control) group. Three weeks after ovariectomy, animals received two daily subcutaneous injections of EB or the oil vehicle. Animals then received intraperitoneal (ip) injections of ghrelin (6.0 or 12.0 nmol) or saline during the nocturnal and diurnal periods three days after the first injection of estradiol or oil. Food intake, meal size, and meal number were determined during the 2-hour period following ghrelin or saline treatments. Ghrelin significantly increased food intake during nocturnal tests in oil-treated but not estradiol-treated rats. The hyperphagic effects of ghrelin on nocturnal food intake were also accompanied by an increase in meal size, and this effect of ghrelin on meal size was attenuated in estradiol-treated females. These findings support the hypothesis that the effects of estradiol on feeding behavior involve an attenuation of orexigenic signals, possibly by modulating the effects of the peripheral ghrelin signal on hypothalamic neuropeptides involved in the control of food intake.