Effect of 2-hydroxyestradiol on binge intake in rats

Abstract

One conundrum of binge eating is that women are more likely to suffer from binge-related disorders, even though estradiol decreases food intake. 2-hydroxyestradiol (2OHE2), an estrogen metabolite, may account for the contradiction, due to possible interference with DA signaling. We hypothesized that 2OHE2 would enhance bingeing in a rodent model. Two cohorts (1 male, 1 female) of 34 non-food-deprived rats were separated into daily control (D) (received an optional source of dietary fat for 20 minutes every day) or bingeing (INT) groups (received fat intermittently, i.e. 20 minutes on Mon, Weds, Fri). During the 5-wk binge induction period, shortening intakes escalated significantly faster in females than in males, such that males consumed significantly less fat/kg body mass than did females after 5 weeks. This result is consistent with the idea that biological differences contribute to sex differences in bingeing. Rats were then injected with 2OHE2 (1.0, 3.0, and 10.0 μg/kg intraperitoneally), vehicle, or 2-methoxyestradiol (2ME2) immediately prior to fat access. Fat intake was significantly stimulated by 2OHE2 only in the INT rats (p<0.03). Furthermore, this effect seemed to be more subtle in females than in males. Thus, 2OHE2 appears to exacerbate binge size. These data suggest a novel biological mechanism for sex differences in the risk of eating disorders.

Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating

“…Female F 2 mice wer more prone to BE ( Fig.2; FigS4A,B )(49-51) which is consistent with human studies(52) and could potentially be explained by the sweetened PF diet(51, 53), neurodevelopmental sex differences in the food reward circuitry and response to PF(54), activational effects of gonadal steroids(50, 52, 55), impulsivity(56), and/or neurobehavioral plasticity that underlies negative reinforcement(57). We did not observe sex differences in PF-CPP in F 2 mice ( Fig.S4C,D ); however, we did observe an increase in freezing episodes in female F 2 mice at 24 h post-BE that was specific to PF training ( Fig.S4F-H ).…”

Factors affecting the ability of baclofen to reduce fat intake in rats

“…Corwin et al, 1998;Wojnicki et al, 2008a;Babbs et al, 2011) have reported that non-fooddeprived rats given brief (20 min to 2 h) intermittent access to vegetable shortening (Mondays, Wednesdays, and Fridays) consume significantly more than rats given brief daily access, regardless of whether the vegetable shortening contains transfats or is transfat free (Wojnicki et al, 2008b). The present results extend these findings to lard, with bingeing observed within the first week of exposure, compared with shortening in which it was not observed until the fourth week.…”

Sex differences in the physiology of eating

“…Because increased plasma levels of estrogens, leading to increases in 2-hydroxy-estradiol, may competitively inhibit dopamine catabolism and increase synaptic dopamine and because altered dopaminergic mechanisms of food reward may contribute to binge eating (89,780), catechol-O-methyltransferase could link estrogens to the propensity to binge. In support of this hypothesis, Babbs et al (29) demonstrated that peripheral injections of 2-hydroxy-estradiol increased eating under binge conditions, but not under normal conditions, in a rat model.…”

“…There is a report that another neurosteroid, 17␣-estradiol, may affect eating (104). Finally, 2-hydroxyestradiol and 2-hydroxyestrone are catabolic products of estrogens that circulate in the blood and may act in the brain to affect food reward (29) (please see…”

“…It is important to replicate these findings and determine whether they can be extended to bulimia nervosa. Finally, further evidence that there is a biological component in the sex difference in binge-eating prevalence comes from fascinating recent rat studies indicating that female rats are more prone to display binge eating-like behavior than are male rats (29,396) (Fig. 17).…”