Sex Differences and Estrous Influences on Oxytocin Control of Food Intake

Central oxytocin potently reduces food intake and is being pursued as a clinical treatment for obesity. While sexually dimorphic effects have been described for the effects of oxytocin on several behavioral outcomes, the role of sex in central oxytocin modulation of feeding behavior is poorly understood. Here we investigated the effects of sex, estrous cycle stage, and female sex hormones (estrogen, progesterone) on central oxytocin-mediated reduction of food intake in rats. Results show that while intracerebroventricular (ICV) oxytocin potently reduces chow intake in both male and female rats, these effects were more pronounced in males than in females. We next examined whether estrous cycle stage affects oxytocin's food intake-reducing effects in females. Results show that ICV oxytocin administration significantly reduces food intake during all estrous cycle stages except proestrous, suggesting that female sex hormones may modulate the feeding effects of oxytocin. Indeed, additional results reveal that estrogen, but not progesterone replacement, in ovariectomized rats abolishes oxytocin-mediated reductions in chow intake. Lastly, oxytocin receptor mRNA (Oxtr) quantification (via quantitative PCR) and anatomical localization (via fluorescent in situ hybridization) in previously established sites of action for oxytocin control of food intake revealed comparable Oxtr expression between male and female rats, suggesting that observed sex and estrous differences may be based on variations in ligand availability and/or binding. Overall, these data show that estrogen reduces the effectiveness of central oxytocin to inhibit food intake, suggesting that sex hormones and estrous cycle should be considered in clinical investigations of oxytocin for obesity treatment.