Non-Genomic Actions of Progestins in Mammalion Reproductive Behavior

点击翻译按钮获取中文摘要

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.