EAGER: The Role of Membrane Progestin Receptors in Progestin-Facilitated Lordosis

类固醇激素在人的一生中对身体和大脑的许多系统的功能都有普遍的影响。重要的是要更充分地了解类固醇是如何发挥作用的，因为有几种潜在的机制可以产生不同的效果。传统观点认为，类固醇与细胞内类固醇受体结合后的作用相对较慢。然而，类固醇激素也可以在细胞膜上以尚未完全了解的方式迅速发挥作用。这些研究的目的是研究关键荷尔蒙孕酮是如何通过作用于潜在的膜靶点--最近发现的膜孕激素受体(MPR)--对大脑和行为产生作用的。在这些实验中，将以大鼠和小鼠为模型，确定MPR在大脑和身体中的表达以及与行为终点的功能相关性。受试者将在大脑中进行MPR操作，通过改变脑部对观察到的行为影响重要的区域的细胞膜孕激素受体的表达或活性来直接研究MPR的作用。因为孕酮是重要的生殖过程的中介，所以不同物种之间的相似性是可以预期的，但不同的MPR在行为上的差异可能会揭示其特异性。将要进行的研究对于了解黄体酮以及其他类固醇激素的作用很重要。这项研究还将为教师提供跨学科的培训，以进一步发展他们在行为神经科学和分子生物学方面的技能。博士后、研究生、本科生和高中生实习生将与两名优秀的科学家合作，在一个项目中探索一个令人兴奋的新调查领域，可以在理解类固醇激素的作用方面取得突破。

Steroid hormones have pervasive effects throughout the lifespan for function of the many systems of the body and brain. It is important to more fully understand how steroids work, given that there are several potential mechanisms for their varied effects. The traditional and well-characterized view is that steroids have relatively slow actions after binding to intracellular steroid receptors. However, steroid hormones can also have rapid effects at the cell membrane in ways that have yet to be fully understood. The purpose of these studies is to investigate how the key hormone progesterone may have actions on the brain and behavior by acting at a potential membrane target, the recently discovered membrane progestin receptors (mPR). In these experiments, the expression of mPRs in the brain and body and the functional relevance with respect to behavioral endpoints will be determined using rats and mice as models. Subjects will have mPR actions in the brain manipulated to directly investigate the role of mPRs by altering membrane progestin receptor expression or activity in brain regions important for the behavioral effects observed. Because progesterone mediates the important process of reproduction, similarities across species are expected, but differences may reveal specificity in the actions of different mPRs. The research to be performed is important for understanding of the actions of progesterone, as well as other steroid hormones. This research will also provide for interdisciplinary training of faculty to further develop their skills in behavioral neuroscience and molecular biology. Post-doctoral, graduate, undergraduate, and high school student trainees will work with two excellent scientists in a project exploring an exciting new area of investigation that can lead to breakthroughs in understanding actions of steroid hormones.