Lindblom Jonas, Kindlundh Anna M S, Nyberg Fred, Bergström Lena, Wikberg Jarl E S
Department of Neuroscience, Division of Pharmacology, Uppsala University, Box 591 BMC, S-751 24 Uppsala, Sweden.
Brain Res. 2003 Oct 3;986(1-2):139-47. doi: 10.1016/s0006-8993(03)03223-2.
Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.
超治疗剂量的合成代谢雄激素类固醇(AASs)对人体新陈代谢有显著影响,并且会抑制大鼠进食并降低其体重增加速率。为了验证AAS代谢综合征伴有中枢黑皮质素系统改变这一假说,我们在给予不同剂量的合成代谢雄激素类固醇癸酸诺龙后,评估了体重、食物摄入量以及下丘脑刺鼠相关蛋白(AgRP)和阿黑皮素原(POMC)的mRNA水平。为了区分类固醇治疗本身引起的变化与食物摄入量和生长速率降低所导致的变化,我们还将癸酸诺龙对AgRP和POMC mRNA表达的影响与正常进食对照组和食物限制对照组进行了比较。我们在此报告,癸酸诺龙的给药特异性降低了弓状核POMC mRNA水平,而不影响AgRP的表达水平。在食物限制对照组中未观察到对POMC表达的影响,排除了观察到的效应仅仅是对食物摄入量和体重降低的反应这一可能性。这些结果增加了AAS滥用的一些代谢和行为后果可能是黑皮质素系统改变所致的可能性。