Kaplowitz E T, Savenkova M, Karatsoreos I N, Romeo R D
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, NY, USA.
Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA.
J Neuroendocrinol. 2016 Feb;28(2):12336. doi: 10.1111/jne.12336.
Prolonged stress and repeated activation of the hypothalamic-pituitary-adrenal axis can result in many sex-dependent behavioural and metabolic changes in rats, including alterations in feeding behaviour and reduced body weight. In adults, these effects of stress can be mimicked by corticosterone, a major output of the hypothalamic-pituitary-adrenal axis, and recapitulate the stress-induced sex difference, such that corticosterone-treated males show greater weight loss than females. Similar to adults, chronic stress during adolescence leads to reduced weight gain, particularly in males. However, it is currently unknown whether corticosterone mediates this somatic change and whether additional measures of neuroendocrine function are affected by chronic corticosterone exposure during adolescence in a sex-dependent manner. Therefore, we examined the effects of non-invasively administered corticosterone (150 or 300 μg/ml) in the drinking water of male and female rats throughout adolescent development (30-58 days of age). We found that adolescent animals exposed to chronic corticosterone gain significantly less weight than controls, which may be partly mediated by the effects of corticosterone on food consumption, fluid intake and gonadal hormone function. Our data further show that, despite similar circulating corticosterone levels, males demonstrate a greater sensitivity to these changes than females. We also found that Npy1 and Npy5 receptor mRNA expression, genes implicated in appetite regulation, was significantly reduced in the ventral medial hypothalamus of corticosterone-treated males and females compared to controls. Finally, parameters of gonadal function, such as plasma sex steroid concentrations and weight of reproductive tissues, were reduced by adolescent corticosterone treatment, although only in males. The data obtained in the present study indicate that chronic corticosterone exposure throughout adolescent development results in significant and sex-dependent somatic and neuroendocrine changes, and the results also provide an experimental framework for further investigating the impact of corticosterone on metabolic and neuroendocrine function during adolescence.
下丘脑 - 垂体 - 肾上腺轴的长期应激和反复激活会导致大鼠出现许多性别依赖性的行为和代谢变化，包括摄食行为改变和体重减轻。在成年大鼠中，应激的这些影响可被皮质酮模拟，皮质酮是下丘脑 - 垂体 - 肾上腺轴的主要产物，并重现应激诱导的性别差异，即皮质酮处理的雄性大鼠比雌性大鼠体重减轻更明显。与成年大鼠类似，青春期的慢性应激会导致体重增加减少，尤其是雄性大鼠。然而，目前尚不清楚皮质酮是否介导这种身体变化，以及青春期慢性皮质酮暴露是否会以性别依赖性方式影响神经内分泌功能的其他指标。因此，我们研究了在雄性和雌性大鼠整个青春期发育过程（30 - 58日龄）中，通过饮水非侵入性给予皮质酮（150或300μg/ml）的影响。我们发现，暴露于慢性皮质酮的青春期动物体重增加明显少于对照组，这可能部分是由皮质酮对食物消耗、液体摄入和性腺激素功能的影响介导的。我们的数据进一步表明，尽管循环皮质酮水平相似，但雄性对这些变化的敏感性高于雌性。我们还发现，与对照组相比，皮质酮处理的雄性和雌性大鼠腹内侧下丘脑参与食欲调节的Npy1和Npy5受体mRNA表达显著降低。最后，青春期皮质酮处理会降低性腺功能参数，如血浆性类固醇浓度和生殖组织重量，不过仅在雄性大鼠中出现这种情况。本研究获得的数据表明，青春期发育过程中慢性皮质酮暴露会导致显著的性别依赖性身体和神经内分泌变化，这些结果也为进一步研究皮质酮对青春期代谢和神经内分泌功能的影响提供了实验框架。
