Mystkowski P, Seeley R J, Hahn T M, Baskin D G, Havel P J, Matsumoto A M, Wilkinson C W, Peacock-Kinzig K, Blake K A, Schwartz M W
Department of Medicine, University of Washington and Veterans Affairs (VA) Puget Sound Health Care System, Seattle, Washington 98104, USA.
J Neurosci. 2000 Nov 15;20(22):8637-42. doi: 10.1523/JNEUROSCI.20-22-08637.2000.
Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen.
黑色素聚集激素（MCH）是一种由下丘脑外侧区（LHA）的神经元产生的促食欲神经肽。由于基因MCH缺乏会导致食欲减退和体脂减少，我们推测MCH神经元可能代表了一条特定的LHA通路，当该通路受到抑制时，会导致某些厌食综合征的发病机制。为了验证这一假设，我们在雄性大鼠的两种高雌激素血症模型（一种高度可重复的厌食范式）中测量了行为、激素和下丘脑神经肽反应。虽然雌激素诱导的体重减轻涉及多个通常有利于体重恢复的系统，但能量限制诱导的MCH mRNA表达的预期增加被选择性地完全消除。这些发现确定MCH神经元是雌激素作用的特定靶点，并表明抑制这些神经元可能导致雌激素的厌食作用。
