Burns Kathleen H, Matzuk Martin M
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Endocrinology. 2002 Aug;143(8):2823-35. doi: 10.1210/endo.143.8.8928.
Fertility in both sexes relies on complex physiological and molecular processes with many levels of regulation, and our ability to alter the mammalian genome using transgenic technology has greatly enhanced our understanding of these processes. There are numerous commonalities in human and mouse physiology, and the list of mouse models recapitulating recognized and idiopathic human reproductive defects is growing at an ever-increasing rate. In this review, we focus on genetic models of gonadotropin actions, summarizing features of transgenic mice that phenocopy defects in gonadotropin production and gonadotropin receptor responses seen in patients. In addition, we provide examples of mouse models with genetic alterations influencing pituitary FSH and LH production and their effects. These include: 1) transgenic mice with aberrations in steroid hormone, inhibin, and activin feedback pathways; 2) knockouts that demonstrate specific in vivo functions of pituitary transcription factors; and 3) models with alterations in other pituitary hormones, IGF-1, and leptin signaling pathways, which affect both the central and peripheral endocrine axis. What we have to learn from these and other models will continue to revise our conceptions of physiology, identify new targets for contraception, and improve our tools for understanding, diagnosing, and treating cases of human endocrinopathies and pathologies of the reproductive tissues.
两性的生育能力都依赖于复杂的生理和分子过程，这些过程存在多个调控层面，而我们利用转基因技术改变哺乳动物基因组的能力极大地增进了我们对这些过程的理解。人类和小鼠的生理学有许多共同之处，能够重现公认的和特发性人类生殖缺陷的小鼠模型列表正以越来越快的速度增长。在这篇综述中，我们聚焦于促性腺激素作用的遗传模型，总结那些模拟患者中促性腺激素产生缺陷和促性腺激素受体反应的转基因小鼠的特征。此外，我们提供了一些基因改变影响垂体促卵泡激素（FSH）和促黄体生成素（LH）产生及其效应的小鼠模型实例。这些实例包括：1）在类固醇激素、抑制素和激活素反馈途径存在异常的转基因小鼠；2）证明垂体转录因子特定体内功能的基因敲除小鼠；3）其他垂体激素、胰岛素样生长因子-1（IGF-1）和瘦素信号通路发生改变的模型，这些改变会影响中枢和外周内分泌轴。我们从这些及其他模型中需要学习的内容将不断修正我们的生理学观念，确定新的避孕靶点，并改进我们理解、诊断和治疗人类内分泌疾病及生殖组织病变病例的工具。
