Sex Differences and Estrous Influences on Oxytocin Control of Food Intake
Sex Differences and Estrous Influences on Oxytocin Control of Food Intake
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DOI：
10.1016/j.neuroscience.2019.10.020
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发表时间：
2020-11-01
期刊：
影响因子：
3.3
通讯作者：
Kanoski, Scott E.
中科院分区：
文献类型：
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作者：
Liu, Clarissa M.;Davis, Elizabeth A.;Kanoski, Scott E.
中枢催产素有效地减少食物摄入，并正在寻求作为肥胖症的临床治疗。虽然已经描述了催产素对几种行为结果的影响的性二态效应，但对性在中枢催产素调节摄食行为中的作用知之甚少。在这里，我们调查了性别，动情周期阶段，和女性性激素（雌激素，孕激素）对中枢催产素介导的大鼠摄食量减少的影响。结果表明，虽然脑室内（ICV）催产素有效地减少了雄性和雌性大鼠的食物摄入量，但这些作用在雄性大鼠中比在雌性大鼠中更明显。接下来，我们研究了发情周期阶段是否影响催产素在雌性动物中的食物摄入减少作用。结果表明，ICV催产素管理显着减少食物的摄入量，在所有的发情周期阶段，除发情前期，表明女性性激素可能会调节催产素的喂养效果。事实上，额外的结果表明，雌激素，而不是孕激素替代，在卵巢切除大鼠废除催产素介导的减少食物摄入量。最后，催产素受体mRNA（Oxtr）的定量（通过定量PCR）和解剖定位（通过荧光原位杂交）在先前建立的催产素控制食物摄入量的作用位点显示，雄性和雌性大鼠之间的Oxtr表达相当，这表明所观察到的性别和发情期的差异可能是基于配体的可用性和/或结合的变化。总体而言，这些数据表明，雌激素降低中枢催产素抑制食物摄入的有效性，这表明性激素和发情周期应考虑催产素治疗肥胖的临床研究。(C)2019年IBRO。由爱思唯尔有限公司出版。保留所有权利。
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. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved.