Fekete Csaba, Singru Praful S, Sanchez Edith, Sarkar Sumit, Christoffolete Marcelo A, Riberio Rogerio S, Rand William M, Emerson Charles H, Bianco Antonio C, Lechan Ronald M
Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Molecular Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.
Endocrinology. 2006 Jan;147(1):520-9. doi: 10.1210/en.2005-0956. Epub 2005 Oct 6.
The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons of the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) and alpha-MSH/cocaine and amphetamine-regulated transcript. Because the central administration of leptin is capable of preventing the inhibitory effects of fasting on TRH mRNA in hypophysiotropic neurons primarily through effects on the arcuate nucleus, we determined whether the continuous administration of 30 mU/d insulin or 648 microg/d glucose into the cerebrospinal fluid by osmotic minipump might also have similar effects on the hypothalamic-pituitary-thyroid axis. As anticipated, the intracerebroventricular infusion of leptin reduced fasting-induced elevations in NPY and AGRP mRNA and increased proopiomelanocortin and cocaine and amphetamine-regulated transcript mRNA in the arcuate nucleus. In addition, leptin prevented fasting-induced reduction in pro-TRH mRNA levels in the paraventricular nucleus and in circulating thyroid hormone levels. In contrast, whereas insulin increased proopiomelanocortin mRNA and both insulin and glucose reduced NPY mRNA in arcuate nucleus neurons, neither prevented the fasting-induced suppression in hypophysiotropic TRH mRNA or circulating thyroid hormone levels. We conclude that insulin and glucose only partially replicate the central effects of leptin and may not be essential components of the hypothalamic-pituitary-thyroid regulatory system during fasting.
禁食期间循环中的瘦素、胰岛素和葡萄糖水平降低，这对下丘脑弓状核的神经元而言是重要的稳态信号，这些神经元会合成神经肽Y（NPY）/刺鼠相关蛋白（AGRP）以及α-促黑素细胞激素（α-MSH）/可卡因和苯丙胺调节转录物（CART）。由于向中枢给药瘦素能够主要通过对弓状核的作用来预防禁食对促甲状腺激素释放激素（TRH）mRNA在促垂体神经元中的抑制作用，因此我们研究了通过渗透微型泵向脑脊液中持续输注30 mU/d胰岛素或648 μg/d葡萄糖是否也会对下丘脑-垂体-甲状腺轴产生类似影响。正如预期的那样，脑室内注入瘦素可降低禁食诱导的弓状核中NPY和AGRP mRNA的升高，并增加阿黑皮素原以及可卡因和苯丙胺调节转录物mRNA的水平。此外，瘦素可防止禁食诱导的室旁核中前TRH mRNA水平以及循环甲状腺激素水平的降低。相比之下，虽然胰岛素增加了阿黑皮素原mRNA的水平，且胰岛素和葡萄糖均降低了弓状核神经元中的NPY mRNA，但两者均未阻止禁食诱导的促垂体TRH mRNA或循环甲状腺激素水平的抑制。我们得出结论，胰岛素和葡萄糖仅部分复制了瘦素的中枢作用，并且在禁食期间可能并非下丘脑-垂体-甲状腺调节系统的必需组成部分。
