Crowley W R, Ramoz G, Torto R, Kalra S P
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
J Neuroendocrinol. 2004 Jul;16(7):637-44. doi: 10.1111/j.1365-2826.2004.01213.x.
The expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP), both of which are important neuropeptides involved in regulation of energy balance and hormone secretion, is up-regulated in the arcuate nucleus during lactation in rodents. The present study tested whether reductions in circulating insulin and/or leptin that occur in lactation provide the critical signals to these systems. Lactating female rats received 3-day infusions of either bovine insulin or recombinant rat leptin via Alzet Osmotic minipumps implanted subcutaneously in regimens designed to restore serum concentrations of these hormones to the higher non-lactating level. Compared to non-lactating rats in diestrus, lactating rats displayed significantly lower serum concentrations of insulin and leptin, and significantly increased NPY peptide concentrations in the paraventricular nucleus (PVN) and median eminence, and AgRP mRNA in the arcuate nucleus. Infusion of leptin in lactating females significantly increased serum concentrations of leptin and significantly reduced NPY concentrations in the PVN and median eminence, and decreased NPY and AgRP mRNAs in the arcuate nucleus. The same effects were produced by infusion of insulin in lactating rats, which restored both insulin and leptin concentrations in serum. The levels of pro-opiomelanocortin mRNA in the arcuate nucleus were not different in non-lactating and lactating females, and were not altered by leptin or insulin treatment. These findings support the hypothesis that the reduction in circulating leptin during lactation contributes to increased expression of NPY and AgRP in hypothalamic systems involved in the behavioural and neuroendocrine adaptations to lactation.
神经肽Y（NPY）和刺鼠相关肽（AgRP）都是参与能量平衡调节和激素分泌的重要神经肽，在啮齿动物哺乳期，它们在弓状核中的表达上调。本研究测试了哺乳期循环胰岛素和/或瘦素的降低是否为这些系统提供关键信号。通过皮下植入的Alzet渗透微型泵，对哺乳期雌性大鼠进行为期3天的牛胰岛素或重组大鼠瘦素输注，输注方案旨在将这些激素的血清浓度恢复到较高的非哺乳期水平。与处于动情间期的非哺乳期大鼠相比，哺乳期大鼠的胰岛素和瘦素血清浓度显著降低，室旁核（PVN）和正中隆起处的NPY肽浓度显著升高，弓状核中的AgRP mRNA也显著升高。给哺乳期雌性大鼠输注瘦素可显著提高血清瘦素浓度，并显著降低PVN和正中隆起处的NPY浓度，同时降低弓状核中的NPY和AgRP mRNA。给哺乳期大鼠输注胰岛素也产生了同样的效果，胰岛素恢复了血清中胰岛素和瘦素的浓度。非哺乳期和哺乳期雌性大鼠弓状核中阿黑皮素原mRNA的水平没有差异，且不受瘦素或胰岛素治疗的影响。这些发现支持了这样一种假说，即哺乳期循环瘦素的降低有助于下丘脑系统中NPY和AgRP表达的增加，这些系统参与了对哺乳的行为和神经内分泌适应。
