Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats.

Hypothalamic-pituitary-gonadal axis function strongly influences feeding and body weight in cycling females in many species. To test the sufficiency of cyclic variations in plasma estradiol to reproduce normal patterns of spontaneous feeding, food intake, and body weight, ovariectomized Long-Evans rats were subcutaneously injected every fourth day with 2 microg estradiol benzoate or with the oil vehicle alone. Cyclic estradiol treatment completely normalized the trajectory of body weight gain and total food intake through seven treatment cycles. The hyperphagia of ovariectomized rats was expressed as an increase in spontaneous meal size. Meal frequency decreased, but not enough to compensate for the increase in meal size. Estradiol treatment normalized both parameters. In addition, cyclic estradiol treatment produced a further phasic decrease in meal size (and increase in meal frequency) and a decrease in food intake during the second night after injection. This phasic change is similar to the feeding changes occurring during estrus in intact rats. Sexual receptivity was measured during the eighth estradiol treatment cycle, 4 h after injection of 0.5 mg progesterone. Lordosis scores at the time of the treatment cycle modeling estrus were maximal, and scores at the time modeling diestrus were slightly increased over those of rats that did not receive estradiol. Finally, plasma estradiol levels, measured during the ninth treatment cycle, revealed a near-normal cyclic pattern of plasma estradiol levels. These results provide the first demonstration that the induction of a cyclic, near-physiological pattern of plasma estradiol is sufficient to maintain normal levels of body weight, spontaneous feeding patterns, total food intake, and (together with progesterone) sexual receptivity in ovariectomized rats.