Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, United States; Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, United States.
Department of Biological Sciences, Human and Evolutionary Biology Section, University of Southern California, Los Angeles, CA, United States.
Neuroscience. 2020 Nov 1;447:63-73. doi: 10.1016/j.neuroscience.2019.10.020. Epub 2019 Nov 15.
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.
中枢催产素能显著减少食物摄入，目前正在被探索作为肥胖的临床治疗方法。虽然催产素对几种行为结果的作用已经表现出性别二态性，但中枢催产素调节摄食行为的性别作用仍知之甚少。在这里，我们研究了性别、发情周期阶段和女性性激素（雌激素、孕激素）对大鼠中枢催产素介导的摄食减少的影响。结果表明，虽然脑室（ICV）催产素能强烈减少雄性和雌性大鼠的普通食物摄入量，但这些作用在雄性大鼠中比在雌性大鼠中更为明显。我们接下来检查了发情周期阶段是否会影响催产素对雌性的摄食减少作用。结果表明，ICV 催产素给药在除发情前期外的所有发情周期阶段均显著减少食物摄入，这表明女性性激素可能调节催产素的摄食作用。事实上，进一步的结果表明，在去卵巢大鼠中，雌激素而不是孕激素替代物会消除催产素介导的普通食物摄入量减少。最后，通过定量 PCR 对先前确定的催产素控制食物摄入作用部位进行催产素受体 mRNA（Oxtr）定量（通过定量 PCR）和解剖定位（通过荧光原位杂交），以及在雄性和雌性大鼠之间进行比较，发现 Oxtr 表达相当，这表明观察到的性别和发情周期差异可能基于配体可用性和/或结合的变化。总的来说，这些数据表明，雌激素降低了中枢催产素抑制食物摄入的有效性，这表明在肥胖症治疗中对催产素进行临床研究时，应考虑性激素和发情周期。
