HORMONES, IMMEDIATE EARLY PROTEINS AND BEHAVIOR

描述(摘自申请者的摘要)：卵巢类固醇 雌激素和黄体酮调节生理和行为， 包括发情行为，在大鼠、豚鼠等物种中。这个 这项研究的长期目标是确定神经元事件 这会导致黄体酮诱导的行为改变。大量的 有证据支持这样一种观点，即黄体酮的一个作用机制 大脑是通过与孕激素结合并随后激活孕激素来实现的 受体，然后可能作为基因表达的调节器。 一种已被用于研究神经元星座的方法 对类固醇激素的反应是使用即刻的表达 早期基因蛋白，如Fos，作为反应神经元的标志。在 拟议的工作，大鼠大脑中受影响的神经元数量 通过雌二醇和黄体酮的治疗，将通过 Fos等即刻早期基因蛋白的表达。那么它将会是 确定特定的孕激素敏感神经元是否有细胞核 可能介导这种反应的孕激素受体，它将被确定 孕激素受体是否对孕酮的直接作用是必需的 神经元反应。最后，将确定是否诱导 即刻早期基因蛋白，如Fos，与 孕酮影响神经元反应的过程，导致 生殖行为的改变。 将使用多种方法。将使用行为方法来 量化孕酮和抑制黄体生成素的作用 孕酮诱导发情行为的即刻早期蛋白表达。 神经解剖学方法将被用来描述 对黄体酮有反应的神经元。颅脑手术在临床上的应用 抑制剂也将被使用，包括黄体酮拮抗剂 孕激素受体和反义寡核苷酸将阻断 孕激素受体和Fos的表达。这是它的一个显著特点 工作是，所有这些都将在与行为相关的背景下完成； 也就是说，激素治疗将被证明是最低限度的。 可靠地促进发情行为表达所需的剂量。

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.