Gregory Christopher W, Atwood Craig S, Smith Mark A, Bowen Richard L
Voyager Pharmaceutical Corporation, Raleigh, NC 27615, USA.
Curr Pharm Des. 2006;12(6):685-90. doi: 10.2174/138161206775474288.
A significant amount of research has been focused on the relationship between hormones and Alzheimer's disease. However, the majority of this work has been on estrogen and more recently testosterone. A serendipitous patient encounter led one of us (RLB) to question whether other hormones of the hypothalamic-pituitary-gonadal axis could be playing a role in the pathogenesis of Alzheimer's disease. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum luteinizing hormone concentrations. Indeed, there is growing evidence that the gonadotropin, luteinizing hormone, which regulates serum estrogen and testosterone concentrations, could be an important causative factor in the development of Alzheimer's disease. This review provides information supporting the "gonadotropin hypothesis," puts forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of Alzheimer's disease, and discusses potential therapeutic anti-gonadotropin compounds.
大量研究聚焦于激素与阿尔茨海默病之间的关系。然而，这项工作大部分集中在雌激素上，最近则是睾酮。一次偶然的患者接触让我们中的一人（RLB）质疑下丘脑 - 垂体 - 性腺轴的其他激素是否可能在阿尔茨海默病的发病机制中起作用。生殖功能随年龄的下降导致血清雌激素和睾酮浓度急剧降低，同时血清促黄体生成素浓度出现同样显著的代偿性升高。事实上，越来越多的证据表明，调节血清雌激素和睾酮浓度的促性腺激素——促黄体生成素，可能是阿尔茨海默病发展的一个重要致病因素。本综述提供了支持“促性腺激素假说”的信息，提出了血清促黄体生成素浓度变化如何导致阿尔茨海默病发病机制的新机制，并讨论了潜在的抗促性腺激素治疗化合物。
