Physiologic Mechanisms of Estradiol's Effects on Eating
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, 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.
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. 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. Administration of estradiol into the medial preoptic area also reduced eating in oophorectomized rats, but again this effect was not evident under slightly different conditions.
Only fragmentary information is available regarding the neurochemical mediation of estradiol's inhibitory effects on eating. Increasing evidence has implicated corticotropin-releasing factor (CRF) in the inhibitory control of eating, both in the context of and independent of stress. Because intraventricular injection of a selective CRF antagonist blocked the inhibitory effect of peripheral estradiol on eating, it is thought that CRF may be involved in estradiol's action on eating. Chronic intraventricular infusion of CRF did not, however, alter daily food intake in non-oophorectomized female rats.
Neuropeptide Y (NPY), delivered into the PVN and/or the adjacent perifornical hypothalamus, potently stimulates eating in animals. In oophorectomized rats, chronic estradiol treatment that reduced food intake decreased NPY concentration in the PVN but not in other areas of the brain. The effect was selective in that concentrations of beta-endorphin, another neurochemical orexigen, were unchanged in any of the areas probed. In a complementary experiment, it was demonstrated that estradiol treatment reduced the orexigenic potency of intrahypothalamic injections of large doses of NPY.
The brain serotonin 5-hydroxytryptophan (5-HT) is another neurochemical that should be considered in the investigation of estradiol's eating effects. Antidepressant 5-HT agonists have been reported to decrease the frequency of binges in bulimic patients, apparently independent of their effects on mood. Furthermore, depletion of tryptophan, the amino acid precursor of 5-HT, increased meal size in bulimic patients.
Medscape General Medicine. 1998;1(3) © 1998
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