HORMONES, IMMEDIATE EARLY PROTEINS AND BEHAVIOR

描述（改编自申请人的摘要）：卵巢类固醇 激素，雌二醇和孕酮，调节生理和行为， 包括大鼠、豚鼠和其他物种的发情行为。 的 这项研究的长期目标是确定神经元事件 从而导致胆固醇引起的行为改变。 大量的 有证据支持这样的观点，孕酮在体内起作用的一种机制是， 大脑是通过结合并随后激活， 受体，然后可以作为基因表达的调节器。 研究神经元群的一种方法是 对类固醇激素有反应的是使用立即表达的 早期基因蛋白，如Fos，作为反应神经元的标记。 在 提出的工作，在大鼠大脑中的神经元，这是影响人口 通过雌二醇和孕酮治疗， Fos和其他立即早期基因蛋白的表达。 然后它将 确定特定的胆固醇敏感神经元是否具有细胞核 可能介导的反应，它将被确定 如果孕激素受体对于孕激素的直接作用是必需的， 神经元反应 最后，将确定是否诱导 立即早期基因蛋白质，如Fos，是因果关系， 孕酮影响神经元反应的过程，导致 生殖行为的改变。 将使用各种方法。 行为方法将用于 量化孕酮和抑制 炔雌醇诱导的发情行为即刻早期蛋白表达。 将使用神经解剖学方法来表征以下人群： 对孕酮有反应的神经元 颅内应用 也可使用抑制剂，包括阻断孕酮受体的孕酮拮抗剂， 受体和反义寡核苷酸，这将阻断 β-淀粉样蛋白受体和Fos.这其中的一个显著特点是 工作是，这一切都将在一个行为相关的背景下进行; 也就是说，将使用激素治疗，这是最小的 促进可靠表达发情行为所需的剂量。

DESCRIPTION (Adapted from applicant's abstract): The ovarian steroid hormones, estradiol and progesterone, regulate physiology and behavior, including estrous behavior, in rats, guinea pigs and other species. The long-term objective of this research is to determine the neuronal events that result in progesterone-induced changes in behaviors. A great deal of evidence supports the idea that one mechanism by which progesterone acts in the brain is via binding to, and subsequent activation of, progestin receptors, which then may act as regulators of gene expression. One approach that has been taken to study the constellation of neurons responsive to steroid hormones is the use of the expression of immediate early gene proteins, such as Fos, as markers for responsive neurons. In the proposed work, the population of neurons in the rat brain that is influenced by treatment with estradiol and progesterone will be delineated through the expression of Fos and other immediate early gene proteins. It will then be determined if particular progesterone-sensitive neurons have cell nuclear progestin receptors that may mediate the response, and it will be determined if progestin receptors are essential for direct effects of progesterone on neuronal response. Finally it will be determined if the induction of immediate early gene proteins, such as Fos, is causally related to the process by which progesterone influences neuronal response, resulting in changes in reproductive behaviors. A variety of methods will be used. Behavioral approaches will be used to quantify the effects of progesterone and of inhibition of progesterone-induced immediate early protein expression on estrous behavior. Neuroanatomical approaches will be used to characterize the populations of neurons that are responsive to progesterone. Intracranial application of inhibitors will also be used, including progesterone antagonists which block progestin receptors and antisense oligonucleotides which will block the expression of progestin receptors and Fos. A distinctive feature of this work is that it will all be done within a behaviorally-relevant context; that is, hormonal treatments will be used which are shown to be the minimal doses necessary to facilitate reliably the expression of estrous behaviors.