McKibbin P E, Cotton S J, McCarthy H D, Williams G
Department of Medicine, University of Liverpool, UK.
Life Sci. 1992;51(16):1301-7. doi: 10.1016/0024-3205(92)90020-p.
Neuropeptide Y (NPY) is a major hypothalamic peptide which is implicated in the regulation of energy balance and in the activation of the hypothalamo-pituitary adrenal axis. This study aimed primarily to determine the effects on regional hypothalamic NPY levels, of catabolism and weight loss induced in rats by the synthetic glucocorticoid, dexamethasone, injected daily at a dose of 0.4 mg/kg for 7 days. NPY concentrations were significantly raised in the paraventricular nucleus (PVN) of male Wistar rats (45%, p = 0.009; n = 10) compared with saline-injected controls (n = 10). Body weight (p less than 0.001) and food intake (p less than 0.001) were significantly reduced, plasma insulin concentrations were increased (p less than 0.001), but there was no change in glucose concentrations. Chronic dexamethasone treatment did not cause the marked NPY increases in the arcuate nucleus (ARC) and other hypothalamic regions which have been observed in other catabolic states causing weight loss. One possible explanation is the high insulin levels induced by dexamethasone, which may have prevented compensatory hyperphagia by suppressing an increase in hypothalamic NPYergic activity. We also examined the acute effects of a single dexamethasone injection on regional hypothalamic levels, to determine whether the drug had a direct action separate from that due to sustained weight loss. In the acute study, groups of rats (n = 7) were examined at 4 h after a single injection of dexamethasone or saline. NPY concentrations were significantly increased in the lateral hypothalamic area (LHA), (60%, p = 0.008) when compared with saline-injected controls, but there was no change in body weight or glucose or insulin concentrations during the 4h interval. Altered transport or release of NPY in the lateral hypothalamic area may be a result of acute feedback regulation by glucocorticoids on the hypothalamus.
神经肽Y（NPY）是一种主要的下丘脑肽，与能量平衡的调节以及下丘脑 - 垂体 - 肾上腺轴的激活有关。本研究主要目的是确定，以0.4mg/kg的剂量每日注射合成糖皮质激素地塞米松，连续注射7天诱导大鼠分解代谢和体重减轻后，对下丘脑区域神经肽Y水平的影响。与注射生理盐水的对照组（n = 10）相比，雄性Wistar大鼠室旁核（PVN）中的神经肽Y浓度显著升高（45%，p = 0.009；n = 10）。体重（p < 0.001）和食物摄入量（p < 0.001）显著降低，血浆胰岛素浓度升高（p < 0.001），但血糖浓度没有变化。慢性地塞米松治疗并未导致弓状核（ARC）和其他下丘脑区域出现在其他导致体重减轻的分解代谢状态中所观察到的显著神经肽Y增加。一种可能的解释是地塞米松诱导的高胰岛素水平，这可能通过抑制下丘脑神经肽Y能活性的增加来阻止代偿性多食。我们还研究了单次注射地塞米松对下丘脑区域水平的急性影响，以确定该药物是否具有独立于持续体重减轻的直接作用。在急性研究中，在单次注射地塞米松或生理盐水后4小时检查大鼠组（n = 7）。与注射生理盐水的对照组相比，下丘脑外侧区（LHA）的神经肽Y浓度显著增加（60%，p = 0.008），但在4小时间隔内体重、血糖或胰岛素浓度没有变化。下丘脑外侧区神经肽Y转运或释放的改变可能是糖皮质激素对下丘脑急性反馈调节的结果。
