Non-Genomic Actions of Progestins in Mammalion Reproductive Behavior

Cheryl Anne Frye博士，提案号0316083，黄体酮在VTASteroid中的非基因组作用激素，如雌二醇和黄体酮，主要的女性性类固醇，传统上被认为是通过大脑中位于细胞内的特定类固醇受体的作用来调节行为。黄体酮介导交配行为的机制部分独立于大脑腹侧被盖区（VTA）的细胞内黄体酮受体的经典行为，该区域对激励和强化很重要。本研究的中心目标是阐明类固醇介导行为的非传统作用。使用的主要方法是行为学和生物化学。首先，孕激素作用的假定底物在VTA中被操纵，并对交配行为的影响进行了检查。那些在黄体酮促进的交配行为中产生一致变化的操作被认为是黄体酮机制的基础。其次，这些底物和黄体酮对它们的影响在VTA组织中进行生化测量。目前的研究将测试黄体酮是否通过膜GABAA和/或多巴胺受体在VTA中起作用。如果GABAA和/或多巴胺受体是VTA中孕酮的机制，那么阻断VTA中的这些受体将减弱孕酮促进的交配行为。此外，在服用或不服用黄体酮的啮齿动物中，VTA中GABAA和/或多巴胺受体的差异是可以预期的。值得注意的是，GABAA和多巴胺受体与其他情感和动机行为有关，这些行为也可能与生殖和交配有关。这项研究将有助于揭示类固醇激素（如黄体酮）在大脑中起作用并影响行为的非传统机制。这些研究的每个方面都将包括本科生，其中一些人将共同发表论文。

Cheryl Anne Frye, Ph.D., proposal number 0316083, Progestins' non-genomic actions in the VTASteroid hormones, such as estradiol and progesterone, the primary female sex steroids, are traditionally understood to mediate behavior through actions in the brain at specific steroid receptors that are located inside of cells. Progesterone's mechanisms to mediate mating behavior occur in part, independent of these classic actions at intracellular progestin receptors in an area of the brain, called the Ventral Tegmental Area (VTA), which is important for motivation and reinforcement. The central goal of the present research is to elucidate non-traditional actions of steroids that mediate behavior. The primary approaches used are behavioral and biochemical. First, putative substrates for progestins' actions are manipulated in the VTA and effects on mating behavior are examined. Those manipulations that produce consistent changes in progesterone-facilitated mating behavior are considered substrates for progesterone's mechanisms. Second, these substrates and progesterone's effects on them are measured biochemically in tissues from the VTA. The present studies will test whether progesterone has actions in the VTA via membrane GABAA and/or dopamine receptors. If GABAA and/or dopamine receptors are mechanisms for progesterone in the VTA, then blocking these receptors in the VTA will attenuate progesterone-facilitated mating behavior. Further, differences in GABAA and/or dopamine receptors in the VTA would be expected in rodents with or without progesterone. Notably, GABAA and dopamine receptors have been implicated in other affective and motivated behaviors, which may also be involved in reproduction and mating. This research will help to reveal non-traditional mechanisms by which steroid hormones, such as progesterone, work in the brain and to affect behavior. Every aspect of these studies will include undergraduate students several of which who will co-author publications.