Department of Internal Medicine I, Luebeck University, Germany.
Am J Physiol Endocrinol Metab. 2010 Feb;298(2):E237-44. doi: 10.1152/ajpendo.00408.2009. Epub 2009 Nov 17.
ACTH and alpha-melanocyte-stimulating hormone (alpha-MSH) are both consecutively processed from proopiomelanocortin (POMC), which is synthesized in hypothalamic arcuate neurons innervating the paraventricular nuclei (PVN). POMC secretion/synthesis is regulated by energy availability. ACTH and alpha-MSH bind with equal affinity to melanocortin-4 receptors and elicit similar effects on signal transduction in-vitro. Endogenous alpha-MSH thus far is believed to be the major physiological agonist and to act in an anorexigenic manner. Until now, it was fully unknown whether endogenous ACTH is also involved in the regulation of appetite and food intake. In this study in rats, we now show that icv ACTH as well as alpha-MSH possess anorexigenic effects in the PVN or areas in close proximity in vivo and that the effect of ACTH is direct and not mediated via alpha-MSH. We investigated the roles of endogenous ACTH and alpha-MSH by PVN application of the respective antibodies under different physiological conditions. In satiated rats with high levels of ACTH and alpha-MSH in the PVN, antibody administration increased food intake and body weight gain; hungry animals were unaffected. Finally, repeated injections of ACTH antibodies into PVN resulted in persistently increased food intake during the light period. These data now provide robust evidence that endogenous ACTH without further processing acts in the PVN or areas in close proximity to reduce food intake under conditions of feeding-induced satiety.
促肾上腺皮质激素（ACTH）和α-黑素细胞刺激素（α-MSH）均由前阿黑皮素原（POMC）连续加工而成，而 POMC 则由投射到室旁核（PVN）的下丘脑弓状核神经元合成。POMC 的分泌/合成受到能量供应的调节。ACTH 和 α-MSH 与黑素皮质素受体 4 的亲和力相等，并在体外引发相似的信号转导效应。迄今为止，内源性 α-MSH 被认为是主要的生理激动剂，并发挥厌食作用。到目前为止，人们还完全不清楚内源性 ACTH 是否也参与了食欲和食物摄入的调节。在这项针对大鼠的研究中，我们现在表明，脑室注射 ACTH 和 α-MSH 均具有在 PVN 或体内附近区域的厌食作用，并且 ACTH 的作用是直接的，而不是通过 α-MSH 介导的。我们在 PVN 应用相应的抗体，在不同的生理条件下，研究了内源性 ACTH 和 α-MSH 的作用。在 PVN 中 ACTH 和 α-MSH 水平较高的饱食大鼠中，抗体给药增加了食物摄入量和体重增加；饥饿动物不受影响。最后，反复向 PVN 注射 ACTH 抗体导致在光照期间持续增加食物摄入量。这些数据现在提供了有力的证据，表明内源性 ACTH 无需进一步加工即可在 PVN 或附近区域发挥作用，以在进食诱导的饱食状态下减少食物摄入。
