Lechan Ronald M, Fekete Csaba
Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tufts-New England Medical Center, Boston, MA 02111, USA. rlechan@tufts-nemc
Peptides. 2006 Feb;27(2):310-25. doi: 10.1016/j.peptides.2005.01.033. Epub 2005 Nov 28.
The melanocortin signaling system is orchestrated by two, independent groups of neurons in the hypothalamic arcuate nucleus with opposing functions that synthesize either alpha-melanocyte stimulating hormone (alpha-MSH) or agouti-related protein (AGRP). These neurons exert regulatory control over hypophysiotropic TRH neurons in the hypothalamic paraventricular nucleus (PVN) at least in part through direct, overlapping, monosynaptic projections to the PVN. Alpha-MSH has an activating effect on hypophysiotropic TRH neurons via the phosphorylation of CREB, and when administered exogenously, can completely reverse fasting-induced suppression of TRH mRNA in the PVN. AGRP has a potent inhibitory effect on the hypothalamic-pituitary-thyroid axis in normally fed animals, mediated through actions at melanocortin 4 receptors. Inhibition of the HPT axis by fasting may be explained by inhibition of melanocortin signaling as a result of a reduction in alpha-MSH and increase in AGRP. Neuropeptide Y may also modulate the effects of the melanocortin signaling system during fasting by potentiating the inhibitory actions of AGRP on hypophysiotropic TRH neurons to prevent the phosphorylation of CREB and through direct inhibitory effects on alpha-MSH-producing neurons in the arcuate nucleus.
黑皮质素信号系统由下丘脑弓状核中两组独立的、功能相反的神经元协调，这两组神经元分别合成α-黑素细胞刺激素（α-MSH）或刺鼠相关蛋白（AGRP）。这些神经元至少部分通过直接、重叠的单突触投射到下丘脑室旁核（PVN），对下丘脑促垂体区的促甲状腺激素释放激素（TRH）神经元发挥调节控制作用。α-MSH通过CREB的磷酸化对下丘脑促垂体区的TRH神经元产生激活作用，当外源性给予时，可完全逆转禁食诱导的PVN中TRH mRNA的抑制。在正常进食的动物中，AGRP对下丘脑-垂体-甲状腺轴具有强大的抑制作用，通过作用于黑皮质素4受体介导。禁食对下丘脑-垂体-甲状腺轴的抑制作用可能是由于α-MSH减少和AGRP增加导致黑皮质素信号传导受到抑制所致。神经肽Y也可能在禁食期间通过增强AGRP对下丘脑促垂体区TRH神经元的抑制作用，以防止CREB磷酸化，并通过对弓状核中产生α-MSH的神经元的直接抑制作用，来调节黑皮质素信号系统的作用。
