Blache D, Adam C L, Martin G B
Faculty of Agriculture (Animal Science), The University of Western Australia, 35 Stirling Highway, Crawley 6009, Western Australia.
Reprod Suppl. 2002;59:219-33.
We have been using mature male sheep to study the ways in which nutrition affects reproduction, with a focus on the brain-pituitary axis and, in particular, GnRH activity. The sheep model has four major advantages for such studies. Firstly, sheep are large enough to support long periods of frequent serial sampling of peripheral blood, hypophyseal portal blood and cerebrospinal fluid from the cerebral ventricles. Importantly, this can be done with freely moving animals and, thus, avoids many of the potential complications associated with restraint. The second advantage, particularly relevant to nutrition-reproduction interactions, is the vast history of nutritional research for this species, providing us with techniques (for example, gut cannulation) and an extensive database on the requirements of sheep for energy, protein and specific dietary components such as amino acids, fatty acids and trace elements. Thirdly, subtle manipulations of diet can be used that cover the range seen in the real world, where animals (including humans) rarely encounter the uninterrupted, ad libitum food supplies that are normal for laboratory animals. Within this normal range of conditions, clear reproductive outcomes can be measured without resorting to starvation and both short- and long-term responses can be studied. Finally, the sheep model has an intrinsic economic relevance and findings from sheep can be transposed readily to other agricultural mammals. The sheep model is also relevant to human biology, often directly, but also indirectly because it often leads us to question the significance of findings from studies with rodents. Using mature male sheep to study the reproductive endocrine responses to acute and chronic changes in diet, we have shown that glucose does not appear to be involved directly, but that fatty acids can stimulate GnRH-dependent pathways that initiate changes in testicular function. Our work also indicates that GnRH-independent (perhaps also neuroendocrine) mechanisms may be involved. In the brain, it seems likely that intracerebral insulin and orexin are important mediators of the GnRH response to nutritional changes, but it is unlikely that leptin plays a role, at least in mature animals.
我们一直在使用成年雄性绵羊来研究营养影响繁殖的方式，重点关注脑垂体轴，尤其是促性腺激素释放激素（GnRH）的活性。绵羊模型在这类研究中有四个主要优点。首先，绵羊体型足够大，能够支持对其外周血、垂体门脉血和脑室脑脊液进行长时间频繁的连续采样。重要的是，这可以在自由活动的动物身上进行，从而避免了许多与限制相关的潜在并发症。第二个优点，尤其与营养 - 繁殖相互作用相关，是针对该物种有着大量的营养研究历史，为我们提供了技术（例如肠道插管）以及关于绵羊对能量、蛋白质和特定饮食成分（如氨基酸、脂肪酸和微量元素）需求的广泛数据库。第三，可以对饮食进行细微调整，涵盖现实世界中所见到的范围，在现实世界中，动物（包括人类）很少能获得实验室动物通常所享用的不间断的随意食物供应。在这个正常条件范围内，可以测量到明确的繁殖结果，而无需诉诸饥饿，并且可以研究短期和长期反应。最后，绵羊模型具有内在的经济相关性，从绵羊研究中获得的结果可以很容易地应用到其他农业哺乳动物身上。绵羊模型也与人类生物学相关，通常是直接相关，但也有间接相关，因为它常常促使我们质疑啮齿动物研究结果的意义。通过使用成年雄性绵羊来研究饮食急性和慢性变化对生殖内分泌的反应，我们已经表明葡萄糖似乎不直接参与其中，但脂肪酸可以刺激依赖GnRH的途径，从而引发睾丸功能的变化。我们的工作还表明，可能涉及不依赖GnRH的（也许也是神经内分泌的）机制。在大脑中，脑内胰岛素和食欲素似乎很可能是GnRH对营养变化反应的重要介质，但瘦素至少在成年动物中不太可能发挥作用。
