Flavor

Flavor is the dominant positive feedback control of meal size. Sweet taste is a clear and experimentally accessible example of the stimulatory effect of preferred flavor on ingestion in animals and humans. Studies of estradiol and the positive feedback effects of sweet taste have produced inconsistent results, perhaps in part because they have not adequately separated oropharyngeal from postingestive food stimuli. When this confound is avoided, estradiol has no effect on eating, which indicates that estradiol does not affect the stimulatory contribution of the positive feedback of sweet taste to meal size.[39,40]

In 1 trial, ingestion of sucrose was studied in non-oophorectomized rats, oophorectomized rats, and oophorectomized rats treated with estradiol. Estradiol was delivered with subcutaneous implants of 10% estradiol in cholesterol. Results showed no change in initial rate of ingestion.[40] However, the rate of ingestion of sucrose for oophorectomized subjects 2 to 4 minutes after meal onset was higher than that for non-oophorectomized subjects. Estradiol treatment reversed this effect. The lack of effect on licking during minute 1 of the meal indicates that the positive orosensory feedback of the sucrose was unaffected by estradiol


Gut Peptides

Peptides released from the gut during meals are a crucial part of the mechanism by which preabsorptive food stimuli control meal size.[14] Among the strongest candidates for gut peptide satiety signals are cholecystokinin (CCK), bombesin-like peptides, glucagon, insulin, and amylin. Each of these is released by preabsorptive food stimuli (especially intestinal-phase stimuli) during the meal, and each has been implicated as a feedback signal for the direct control of meal size.

CCK is the best understood of these peptides. Suppression of endogenous CCK increased meal size in rats by way of peripheral administration of selective antagonists of the visceral type CCKA receptor.[41] Meal size was increased in rats by antagonism of endogenous CCK's actions by peripheral administration of selective blockers of the visceral type CCKA receptor.[41]

In humans, double-blind tests showed that CCK infusion reduces meal size without interfering with the normal subjective experience of satiety.[41] CCK is the only satiety signal for which a significant amount of research on sex differences has been done. Two early reports suggested that estradiol may decrease CCK's satiating potency[42,43]; however, sample sizes were small, doses of CCK-8 and estradiol were suprapharmacologic, and data were variable. When the problems with methodology were eliminated, estradiol increased exogenous CCK-8's satiating potency in oophorectomized rats[44-46] . In 1 study, oophorectomized rats received either chronic subcutaneous estradiol treatment, or an oil vehicle alone after 17 hours of food deprivation. When the rats were intraperitoneally injected with CCK-8 just before the test meal, there was an increase in the satiating potency of CCK-8 when estradiol treatment was administered.


Furthermore, it was recently demonstrated that the satiating potency of endogenous CCK in non-oophorectomized rats is increased during estrus.[47,48] The degree to which these effects might mirror physiologic changes in disordered eating in women is, of course, uncertain. Interestingly, however, bulimic patients exhibit defects in both the perception of satiety and food-stimulated CCK release.[49]

The potency of glucagon and of 1 bombesin-like peptide, gastric-releasing peptide, may also be increased by estradiol in rats, whereas that of neuromedin B appears not to be.[50] Estradiol's effect on other peptide satiety signals remains to be investigated.

Conclusion
Several lines of investigation have begun to reveal the peripheral and central mechanisms by which estradiol exerts its potent inhibitory effects on eating in rats. If similar mechanisms are present in women, understanding how estradiol inhibits eating may shed light on the basis for the increased vulnerability of women to eating disorders. Bridging the knowledge gap in this area may result in the development of effective therapeutic strategies for these disorders.