Zieba D A, Amstalden M, Williams G L
Animal Reproduction Laboratory, Texas A&M University Agricultural Research Station, 3507 Hwy 59E, Beeville, TX 78102, USA.
Domest Anim Endocrinol. 2005 Jul;29(1):166-85. doi: 10.1016/j.domaniend.2005.02.019. Epub 2005 Apr 19.
Leptin plays an important role in signaling nutritional status to the central reproductive axis of mammals and appears to be at least a permissive factor in the initiation of puberty. The expression and secretion of leptin are correlated with body fat mass and are acutely affected by changes in feed intake. Moreover, circulating leptin increases during pubertal development in rodents, human females and heifers. Effects of leptin are mediated mainly via receptor activation of the JAK-STAT pathway; however, activation of alternative pathways, such as MAP kinase, has also been reported. Although the leptin receptor (LR) has not been found on GnRH neurons, leptin stimulates the release of GnRH from rat and porcine hypothalamic explants. Moreover, leptin increases the release of LH in rats and from adenohypophyseal explants and/or cells from full-fed rats and pigs. In contrast, stimulation of the hypothalamic-gonadotropic axis by leptin in cattle and sheep is observed predominantly in animals and tissues pre-exposed to profound negative energy balance. For example, leptin prevents fasting-mediated reductions in the frequency of LH pulses in peripubertal heifers, augments the magnitude of LH and GnRH pulses in fasted cows, and enhances basal secretion of LH in vivo and from adenohypophyseal explants of fasted cows. However, leptin is incapable of accelerating the frequency of LH pulses in prepubertal heifers, regardless of nutrient status, and has no effect on the secretion of GnRH and LH in full-fed cattle or hypothalamic/hypophyseal explants derived thereof. Similar to results obtained with LH, basal secretion of GH from anterior pituitary explants of fasted, but not normal-fed cows, was potentiated acutely by low, but not high, doses of leptin. Mechanisms through which undernutrition hypersensitize the hypothalamic-gonadotropic axis to leptin may involve up-regulation of the LR. However, an increase in LR mRNA expression is not a requisite feature of heightened adenohypophyseal responses in fasted cattle. To date, leptin has not been successful for inducing puberty in ruminants. Future therapeutic uses for recombinant leptin that exploit states of nutritional hypersensitization, and identification of genetic markers for genotypic variation in leptin resistance, are currently under investigation.
瘦素在向哺乳动物的中枢生殖轴传递营养状态信号方面发挥着重要作用，并且似乎至少是青春期启动的一个允许因子。瘦素的表达和分泌与体脂量相关，并受到采食量变化的急性影响。此外，在啮齿动物、人类女性和小母牛的青春期发育过程中，循环中的瘦素会增加。瘦素的作用主要通过JAK-STAT途径的受体激活来介导；然而，也有报道称存在其他途径的激活，如丝裂原活化蛋白激酶（MAP激酶）途径。尽管在促性腺激素释放激素（GnRH）神经元上未发现瘦素受体（LR），但瘦素可刺激大鼠和猪下丘脑外植体释放GnRH。此外，瘦素可增加大鼠以及饱食大鼠和猪的腺垂体外植体和/或细胞中促黄体生成素（LH）的释放。相比之下，瘦素对牛和羊下丘脑-促性腺轴的刺激主要在预先经历深度负能量平衡的动物和组织中观察到。例如，瘦素可防止青春期前小母牛因禁食介导的LH脉冲频率降低，增加禁食母牛中LH和GnRH脉冲的幅度，并增强禁食母牛体内以及腺垂体外植体中LH的基础分泌。然而，无论营养状态如何，瘦素都无法加快青春期前小母牛LH脉冲的频率，并且对饱食牛或其来源的下丘脑/垂体外植体中GnRH和LH的分泌没有影响。与LH的结果相似，低剂量而非高剂量的瘦素可急性增强禁食但非正常饲养母牛垂体前叶外植体中生长激素（GH）的基础分泌。营养不良使下丘脑-促性腺轴对瘦素超敏的机制可能涉及LR的上调。然而，LR信使核糖核酸（mRNA）表达的增加并非禁食牛腺垂体反应增强的必要特征。迄今为止，瘦素在反刍动物中诱导青春期尚未成功。目前正在研究利用营养超敏状态的重组瘦素的未来治疗用途，以及鉴定瘦素抵抗基因型变异的遗传标记。
