Swaab Dick F
Netherlands Institute for Brain Research, 1105 AZ, Amsterdam, The Netherlands.
Int Rev Cytol. 2004;240:305-75. doi: 10.1016/S0074-7696(04)40003-5.
A few examples of hypothalamic, peptidergic disorders leading to clinical signs and symptoms are presented in this review. Increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) and decreased activity of the vasopressin neurons in the biological clock and of the thyroxine-releasing hormone (TRH) neurons in the PVN contribute to the signs and symptoms of depression. In men, the central nucleus of the bed nucleus of the stria terminalis (BSTc) is about twice as large and contains twice as many somatostatin neurons as in women. In transsexuals this sex difference is reversed, pointing to a role of this structure in gender. Luteinizing hormone-releasing hormone (LHRH) neurons are formed in the fetal olfactory placade and migrate along the terminal nerve fibers into the hypothalamus. In Kallmann's syndrome the migration process of the LHRH (gonadotropin-releasing hormone) neurons is aborted, which explains the joint occurrence of hypogonadotropic hypogonadism and anosmia in this syndrome. In postmenopausal women, the neurons of the infundibular nucleus hypertrophy and become hyperactive because of the disappearance of the estrogen feedback and contain hyperactive peptidergic neurons. Climacteric flushes may be caused by hyperactivity of the neurokinin-B or LHRH neurons in this nucleus. The hypocretin (orexin) neurons in the perifornical area are involved in sleep. In narcolepsy with cataplexy, a loss of these neurons, probably due to an autoimmune process, is found. Obese subjects with a mutation in the gene that encodes for leptin, the preproghrelin gene, or the alpha-melanocyte-stimulating hormone (alpha-MSH) gene have been described. Decreased numbers and activity of the oxytocin neurons in the PVN may be responsible for the absence of satiety in Prader-Willi syndrome. Moreover, a glucocorticoid receptor polymorphism is associated with obesitas and dysregulation of the hypothalamus-pituitary-adrenal axis. In contrast, two single nucleotide polymorphisms (SNPs) of the AGRP gene have been associated with anorexia nervosa.
本综述介绍了一些导致临床体征和症状的下丘脑肽能紊乱的例子。室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）神经元活性增加，生物钟中血管加压素神经元以及PVN中促甲状腺激素释放激素（TRH）神经元活性降低，这些都导致了抑郁症的体征和症状。在男性中，终纹床核（BSTc）的中央核大约是女性的两倍大，且生长抑素神经元数量是女性的两倍。在变性人中，这种性别差异会逆转，表明该结构在性别方面的作用。促黄体生成素释放激素（LHRH）神经元在胎儿嗅基板中形成，并沿着终末神经纤维迁移至下丘脑。在卡尔曼综合征中，LHRH（促性腺激素释放激素）神经元的迁移过程中断，这解释了该综合征中促性腺激素缺乏性性腺功能减退和嗅觉缺失的共同出现。在绝经后女性中，由于雌激素反馈消失，漏斗核的神经元肥大并变得活跃，且含有活跃的肽能神经元。更年期潮热可能是由该核中神经激肽B或LHRH神经元的过度活跃引起的。穹窿周区的下丘脑分泌素（食欲素）神经元与睡眠有关。在发作性睡病伴猝倒中，发现这些神经元缺失，可能是由于自身免疫过程所致。已经描述了肥胖受试者中编码瘦素、前proghrelin基因或α - 黑素细胞刺激激素（α - MSH）基因发生突变的情况。PVN中催产素神经元数量和活性降低可能是普拉德 - 威利综合征中缺乏饱腹感的原因。此外，糖皮质激素受体多态性与肥胖症以及下丘脑 - 垂体 - 肾上腺轴失调有关。相反，AGRP基因的两个单核苷酸多态性（SNP）与神经性厌食症有关。
