Aubert M L, Pierroz D D, Gruaz N M, d'Allèves V, Vuagnat B A, Pralong F P, Blum W F, Sizonenko P C
Department of Pediatrics, School of Medicine, Geneva, Switzerland.
Mol Cell Endocrinol. 1998 May 25;140(1-2):107-13. doi: 10.1016/s0303-7207(98)00058-6.
The discovery of leptin has generated an extraordinary interest in the field of obesity but also in the understanding of the relationship between metabolic status and the neuroendocrine system. Following the initial demonstration that leptin administration to fasting mice can 'protect' neuroendocrine secretions and prevent the changes that are associated with fasting, the concept has emerged that a normal leptin secretion is a prerequisite for normal neuroendocrine secretions. Several unfavorable metabolic situations are associated with low plasma leptin, increased secretion of hypothalmic neuropeptide Y (NPY), and hypogonadism, and a causal relationship has been evoked. Severe dietary restriction in juvenile female rats is associated with low plasma leptin and sexual immaturity. Cessation of food restriction leads to immediate increase in plasma leptin followed 4 days later by vaginal opening. If food restriction is maintained, central leptin infusion can induce sexual maturation, thus demonstrating that leptin can act as a signal for the onset of puberty. In untreated type-I diabetic rats, hypogonadism is associated with very low plasma leptin and increased hypothalmic NYP synthesis and oestrous cyclicity. Fasting rapidly inhibits growth hormone (GH) secretion in association with low plasma leptin and elevated hypothalmic NPY. Central infusion of leptin to fasting rats was able to completely prevent the collapse of GH secretion and to maintain a normal low NPY synthesis. In summary, normally elevated plasma levels appear to be a prerequisite for normal GH and gonadotropin secretion in the rat. Degradation of metabolic conditions results in a rapid reduction of circulating leptin that could represent the signal for several alterations of neuroendocrine secretions. At the level of the hypothalamus, leptin could act on NPY neurons to transduce part or all of this 'metabolic' message. The possibility that changing plasma levels for leptin also affect peripheral endocrine targets, such as pituitary, ovary, adrenal or pancreas, is likely since these endocrine organs express functional long-term leptin receptors.
瘦素的发现不仅在肥胖领域引发了极大的关注，也促进了人们对代谢状态与神经内分泌系统之间关系的理解。在最初证明向禁食小鼠注射瘦素可以“保护”神经内分泌分泌并防止与禁食相关的变化之后，一种观念逐渐形成，即正常的瘦素分泌是正常神经内分泌分泌的先决条件。几种不良的代谢状况与血浆瘦素水平低、下丘脑神经肽Y（NPY）分泌增加以及性腺功能减退有关，人们推测它们之间存在因果关系。幼年雌性大鼠的严格饮食限制与血浆瘦素水平低和性不成熟有关。停止食物限制会导致血浆瘦素立即增加，4天后阴道开口。如果维持食物限制，中枢注射瘦素可诱导性成熟，从而表明瘦素可作为青春期开始的信号。在未经治疗的I型糖尿病大鼠中，性腺功能减退与极低的血浆瘦素水平、下丘脑NYP合成增加和发情周期有关。禁食会迅速抑制生长激素（GH）分泌，同时血浆瘦素水平低且下丘脑NPY升高。向禁食大鼠中枢注射瘦素能够完全防止GH分泌的崩溃，并维持正常的低NPY合成。总之，正常升高的血浆水平似乎是大鼠正常GH和促性腺激素分泌的先决条件。代谢状况的恶化会导致循环瘦素迅速减少，这可能是神经内分泌分泌发生多种改变的信号。在下丘脑水平上，瘦素可能作用于NPY神经元，以传递部分或全部这种“代谢”信息。由于这些内分泌器官表达功能性的长效瘦素受体，血浆瘦素水平的变化也可能影响外周内分泌靶器官，如垂体、卵巢、肾上腺或胰腺。
