Keisler D H, Daniel J A, Morrison C D
Department of Animal Science, University of Missouri, Columbia 65211, USA.
J Reprod Fertil Suppl. 1999;54:425-35.
Infertility associated with suboptimal nutrition is a major concern among livestock producers. Undernourished prepubertal animals will not enter puberty until they are well fed; similarly, adult, normally cyclic females will stop cycling when faced with extreme undernutrition. Work in our laboratory has focused on how body fat (or adiposity) of an animal can communicate to the brain and regulate reproductive competence. In 1994, the discovery in rodents of the obese (ob) gene product leptin, secreted as a hormone from adipocytes, provided a unique opportunity to understand and hence regulate whole body compositional changes. There is now evidence that similar mechanisms are functioning in livestock species in which food intake, body composition, and reproductive performance are of considerable economic importance. Leptin has been reported to be a potent regulator of food intake and reproduction in rodents. There is evidence indicating that at least some of the effects of leptin occur through receptor-mediated regulation of the hypothalamic protein neuropeptide Y (NPY). NPY is a potent stimulator of food intake, is present at high concentrations in feed-restricted cattle and ewes, and is an inhibitor of LH secretion in these livestock species. In our investigations in sheep, we have cloned a partial cDNA corresponding to the ovine long-form leptin receptor, presumably the only fully active form, and have localized the long-form leptin receptor in the ventromedial and arcuate nuclei of the hypothalamus. Leptin receptor mRNA expression was colocalized with NPY mRNA-containing cell bodies in those regions. We have also determined that hypothalamic leptin receptor expression is greater in feed-restricted ewes than in well-fed ewes. These observations provide a foundation for future investigations into the nutritional modulators of reproduction in livestock.
营养欠佳导致的不育是畜牧生产者主要关注的问题。青春期前营养不良的动物在营养充足之前不会进入青春期；同样，成年后正常发情的雌性动物在面临极度营养不良时会停止发情。我们实验室的工作重点是动物的体脂（或肥胖程度）如何与大脑进行沟通并调节繁殖能力。1994年，在啮齿动物中发现脂肪细胞分泌的肥胖（ob）基因产物瘦素，为理解并进而调节全身成分变化提供了独特的契机。现在有证据表明，类似的机制在畜牧物种中也发挥着作用，在这些物种中，食物摄入量、身体组成和繁殖性能具有相当重要的经济意义。据报道，瘦素是啮齿动物食物摄入和繁殖的有效调节因子。有证据表明，瘦素的至少一些作用是通过受体介导的对下丘脑蛋白质神经肽Y（NPY）的调节来实现的。NPY是食物摄入的有效刺激因子，在限饲的牛和羊体内浓度很高，并且是这些畜牧物种中促黄体生成素分泌的抑制剂。在我们对绵羊的研究中，我们克隆了与绵羊长型瘦素受体相对应的部分cDNA，推测这是唯一的完全活性形式，并已将长型瘦素受体定位在下丘脑的腹内侧核和弓状核中。瘦素受体mRNA表达与这些区域中含有NPY mRNA的细胞体共定位。我们还确定，限饲母羊下丘脑瘦素受体的表达高于营养良好的母羊。这些观察结果为未来研究家畜繁殖的营养调节因子奠定了基础。
