Estrogenic modulation of body weight in female rats is usually thought to result indirectly from estrogenic modulation of food intake. The data presented here suggest, however, that estrogens influence body weight by at least two mechanisms, one of which is independent of changes in food intake. When female rats were ovariectomized (Ovx) and food intake was limited to preoperative levels, the Ovx animals nonetheless gained large amounts of body weight. Although Ovx rats gained more weight than controls on the same amount of food, during 33 hr of food deprivation Ovx and control animals lost body weight at the same rate, which indicates that the prefacing metabolic rates of the two groups were generally similar. Examination of recovery from food deprivation suggested that the rate of weight gain after Ovx was very gradual During the first 40 days after surgery, the ano-nasal lengths of Ovx rats increased twice as fast as the ano-nasal lengths of the intact rats, which suggests a mechanism for the gradual increase in body weight induced by Ovx The body weights of intact rats followed a regular 4-day cycle during ad lib feeding, but when the estrus-associated decrease in food intake was prevented, the cyclic body weight changes were dramatically altered. Thus estrogens appear to regulate body weight by at least two mechanisms' modulation of food intake (cycling females) and modulation of ano-nasal growth or other metabolic processes (Ovx females).

Estrogens have recently been described as being most effective in restraining the food intake and body weight of female rats that face impending obesity. A corollary is that estrogens are more effective in preventing than reversing the body weight gain that accompanies ovariectomy (Ovx). Four experiments examined the effects of estradiol benzoate (EB) on food intake, body weight, ano-nasal length, and body weight to body length ratio (Lee index) of ovariectomized and intact rats maintained on control or high-fat diets, and of Ovx and intact rats that had been reduced by deprivation. Estradiol benzoate was highly effective in preventing the increase in food intake, body weight, and ano-nasal growth after Ovx. It was relatively ineffective in reversing body weight gain after Ovx. However, when ano-nasal length was also considered, EB was effective in returning Ovx rats to an appropriate body weight for their increased ano-nasai length. About 40% of the body weight gain after Ovx appears to be due to skeletal growth and the increased tissue mass necessary to maintain it. Intact rats fed a high-caloric diet did not exhibit an increased rate of ano-nasal growth, which indicates that the skeletal growth that occurs after Ovx is not simply a result of increased food intake. Estradiol benzoate was eventually effective in reducing the body weights of intact rats maintained on a high-fat diet, but it also reduced the body weights of intact control rats. The high-fat diet did not alter the amount of weight gained after Ovx. It is concluded that EB modulates food intake and body weight by multiple mechanisms, one of which is by modulating skeletal growth. The nature of the effect of EB on the body weight of intact rats suggests that this effect occurs by still another mechanism.