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.[25] 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.[26] 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.[27]

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.[18]