Charlton H
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
J Neuroendocrinol. 2008 Jun;20(6):641-6. doi: 10.1111/j.1365-2826.2008.01718.x.
The concept of neurohumoral control of anterior pituitary function championed by Geoffrey Harris was based upon clinical and biological observation backed by rigorous experimental testing. The areas of the brain involved in the control of gonadotrophic hormone synthesis and release were identified by electrical stimulation, lesioning and fibre tract cutting. The medial preoptic area (MPOA) proved to be a major integrating centre, with axon terminals from this region terminating at the median eminence releasing factors into the portal vessels to give a direct route from brain to pituitary. It took over a decade before the gonadotrophic hormone-releasing hormone (GnRH) was isolated, sequenced and synthesised. With antibodies raised against this peptide, the MPOA was identified as a site rich in GnRH neurones and the hormone was detected at high levels in portal blood extracts. A natural knockout of the GnRH gene was discovered in a hypogonadal (hpg) mouse. Hormone injections, gene replacement methods and neural grafting in these mutants all confirmed the central role of GnRH in reproduction. The modern techniques of molecular biology have allowed us to extend our knowledge base. In the last few years the role of kisspeptin and its receptor (GPR54) in the control of the GnRH neurone has added a further level of hypothalamic involvement in the modulation of reproduction.
杰弗里·哈里斯提出的垂体前叶功能神经体液控制概念，是基于严格实验测试支持的临床和生物学观察。通过电刺激、损伤和纤维束切断，确定了大脑中参与促性腺激素合成和释放控制的区域。内侧视前区（MPOA）被证明是一个主要的整合中心，来自该区域的轴突终末在正中隆起处终止，将释放因子释放到门静脉血管中，从而形成从大脑到垂体的直接路径。过了十多年，促性腺激素释放激素（GnRH）才被分离、测序和合成。利用针对该肽产生的抗体，MPOA被确定为富含GnRH神经元的部位，并且在门静脉血提取物中检测到高水平的该激素。在性腺功能减退（hpg）小鼠中发现了GnRH基因的自然敲除。在这些突变体中进行激素注射、基因替代方法和神经移植，都证实了GnRH在生殖中的核心作用。分子生物学的现代技术使我们能够扩展知识库。在过去几年中，亲吻素及其受体（GPR54）在GnRH神经元控制中的作用，为下丘脑在生殖调节中的参与增加了一个新层面。
