Drazen Deborah L, Coolen Lique M, Strader April D, Wortman Matthew D, Woods Stephen C, Seeley Randy J
Department of Psychiatry, Genome Research Institute, University of Cincinnati, 2170 East Galbraith Road, Building 43, Third Floor, Cincinnati, Ohio 45237, USA.
Endocrinology. 2004 Jul;145(7):3404-12. doi: 10.1210/en.2003-1760. Epub 2004 Mar 24.
Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight in rodents and prevents excessive weight gain in many genetic and dietary models of obesity. Glucocorticoids play a key role to promote positive energy balance in normal and pathological conditions, at least in part, by altering the sensitivity to hypothalamic peptides. The hyperphagia after central neuropeptide Y administration, for example, is attenuated by ADX, and there is evidence that glucocorticoids influence both MCH and orexin A activity. In the present study, feeding responses to third ventricular MCH and orexin A were measured in rats after bilateral ADX or sham surgery. ADX rats were significantly less sensitive to the orexigenic action of third ventricular MCH, whereas orexin A-induced hyperphagia was unaffected. Replacement of corticosterone in the drinking water of ADX rats reversed the effects of ADX on MCH sensitivity. Although we found significant populations of glucocorticoid receptors in the lateral hypothalamus, none were colocalized with either MCH or orexin A-containing cell bodies. Furthermore, whereas ADX significantly reduced hypothalamic MCH and orexin gene expression, this could not be restored by glucocorticoids in the drinking water. Collectively, the present data suggest that glucocorticoids may promote food intake in part by potentiating the orexigenic actions of MCH without affecting the actions of orexin A and that glucocorticoids act indirectly to influence the effects of MCH on food intake.
通过肾上腺切除术（ADX）去除糖皮质激素可减少啮齿动物的食物摄入量和体重，并防止许多肥胖的遗传和饮食模型中体重过度增加。糖皮质激素在促进正常和病理状态下的正能量平衡中起关键作用，至少部分是通过改变对下丘脑肽的敏感性来实现的。例如，中枢给予神经肽Y后的食欲亢进会被ADX减弱，并且有证据表明糖皮质激素会影响MCH和食欲素A的活性。在本研究中，在双侧ADX或假手术后测量大鼠对第三脑室MCH和食欲素A的进食反应。ADX大鼠对第三脑室MCH的促食欲作用明显不敏感，而食欲素A诱导的食欲亢进不受影响。在ADX大鼠的饮用水中补充皮质酮可逆转ADX对MCH敏感性的影响。尽管我们在下丘脑外侧发现了大量的糖皮质激素受体，但没有一个与含有MCH或食欲素A的细胞体共定位。此外，虽然ADX显著降低了下丘脑MCH和食欲素基因的表达，但饮用水中的糖皮质激素并不能恢复这种表达。总的来说，目前的数据表明，糖皮质激素可能部分通过增强MCH的促食欲作用而不影响食欲素A的作用来促进食物摄入，并且糖皮质激素通过间接作用来影响MCH对食物摄入的影响。
