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Endocrinology. 2017 Jul 1;158(7):2239-2254. doi: 10.1210/en.2017-00208.

Chronic Corticosterone Treatment During Adolescence Has Significant Effects on Metabolism and Skeletal Development in Male C57BL6/N Mice.

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Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington 99164.
Department of Psychology and Neuroscience and Behavior Program, Barnard College of Columbia University, New York, New York 10027.


Glucocorticoids are potent modulators of metabolic and behavioral function. Their role as mediators in the "stress response" is well known, but arguably their primary physiological function is in the regulation of cellular and organismal metabolism. Disruption of normal glucocorticoid function is linked to metabolic disease, such as Cushing syndrome. Glucocorticoids are also elevated in many forms of obesity, suggesting that there are bidirectional effects of these potent hormones on metabolism and metabolic function. Adolescence is a time of rapid physical growth, and disruptions during this critical time likely have important implications for adult function. The hypothalamic-pituitary-adrenal axis continues to mature during this period, as do tissues that respond to glucocorticoids. In this work, we investigate how chronic noninvasive exposure to corticosterone affects metabolic outcomes (body weight, body composition, insulin, and glucose homeostasis), as well as changes in bone density in both adult and adolescent male mice. Specifically, we report a different pattern of metabolic effects in adolescent mice compared with adults, as well as an altered trajectory of recovery in adolescents and adults. Together, these data indicate the profound influence that adolescent development has on the metabolic outcomes of chronic corticosterone exposure, and describe a tractable model for understanding the short- and long-term impacts of hypercortisolemic states on physiological and neurobehavioral functions.

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