Brain Mechanisms

Studies of estradiol delivery to specific forebrain loci have not yet identified a specific area where estradiol acts to inhibit eating. Possibly the action of estradiol, like its feedback effect on luteinizing hormone secretion,[21] involves simultaneous actions in more than 1 forebrain site. After the observation that implants of crystalline estradiol in the hypothalamus reduced food intake, it was originally hypothesized that estradiol acts in the ventromedial hypothalamic area to inhibit feeding. This hypothesis was soon refuted by demonstrations that implants of dilute estradiol, which did not spread as far from the cannula site, did not affect feeding. Furthermore, peripheral estradiol still reduced feeding after inducing ventromedial hypothalamic lesions.[22]

A more promising site of action appears to be the hypothalamic paraventricular nuclei (PVN). When dilute estradiol (10%-30% estradiol in cholesterol) was implanted into the PVN, food intake and body weight declined in oophorectomized rats. Bilateral lesions of the PVN or blockade of protein synthesis in the PVN by administration of anisomycin blocked the effect of peripheral estradiol on feeding in oophorectomized rats.[22] These results, together with the presence of estradiol receptors in the PVN, suggest that endogenous estradiol may act in the PVN to result in decreased meal size. However, these results have proven difficult to replicate.[23] Administration of estradiol into the medial preoptic area also reduced eating in oophorectomized rats,[24] but again this effect was not evident under slightly different conditions.[22]