This application proposes behavioral and physiological investigations of the mechanisms by which the ovarian steroid hormone, estradiol, modulates feeding in female rats. There are prominent sex differences in food intake in animals and humans. Eating disorders, such an anorexia nervosa and obesity, constitute major health care problems and also display marked sex differences. Unfortunately, the causes of sex differences in appetite and in the pathologies of eating disorders are not well understood. In many situations, meal size appears to be decreased by estradiol. In laboratory rodents, a decrease in meal size follows the pre-estrus increase in circulating estradiol. Similarly, ovariectomy causes an increase in meal size and body weight that can be reversed by peripheral, and perhaps central, estradiol administration. The mechanisms mediating these changes in meal size, however, are unknown. Therefore, this application proposes a series of experiments to determine how peripheral and central estradiol influence the potencies of pregastric, gastric, and intestinal food stimuli that are candidate physiological controls of meal size. The proposal has four specific aims.
Aim 1 pursues a recent demonstration that paraventricular hypothalamic lesions block the decrease in food intake following peripheral estradiol administration in ovariectomized rats by determining whether paraventricular estradiol implants decrease meal size in ovariectomized rats and whether paraventricular lesions block the pre- estrus decrease in meal size in gonadally intact rats.
Aim 2 is to determine the influence of peripheral and central estradiol on the positive pregastric effect of sweet taste that stimulates feeding and on the negative pregastric feedback that inhibits feeding.
Aim 3 is to determine the effects of peripheral and central estradiol on gastric satiety signals, including tests of the putative gastric satiety signal bombesin.
Aim 4 is to determine the influence of peripheral and central estradiol on intestinal satiety signals, including tests of stomach emptying and of pancreatic glucagon. The sensitivity and physiological relevance of the proposed experiments are increased by using a lick-by- lick analysis of the microstructure of ingestion, by testing spontaneous meals as well as scheduled tests meals, and by using a cyclic regimen of estradiol replacement to mimic the natural estrus cycle in ovariectomized rats. The long term goals of the research are to understand the physiological interactions of estradiol with peripheral controls of meal size in rats and to use this information to model the effect of estradiol on appetite and food intake in women and to model how normal or low concentrations of estradiol are involved in the vulnerability of women to eating disorders.
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