CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 大脑中的性类固醇调节生殖行为，具有调节功能 超越了对繁殖的影响。例如，天然和合成雄激素可以 导致精神紊乱，如焦虑和抑郁。雄激素可以 调节特定的细胞底物，如神经肽和生长因子， 关于负责观察到的行为的细胞机制的相关问题 生理或滥用浓度下的变化。神经肽与 与生殖和焦虑有关的行为。神经肽Y和阿片样物质，在 调节生殖行为和焦虑的大脑区域，但它们也被 被证明是受荷尔蒙控制的然而，这些行为中隐含的细胞事件 目前还知之甚少，主要是在体内研究。本提案研究了 生殖和焦虑相关行为的生化基础， 系统将来自内侧视前区和杏仁核复合体的分离细胞暴露于 睾酮和合成代谢雄激素类固醇（AAS），17 <$-甲基睾酮。 培养 细胞将从青春期大鼠中分离，因为青春期是关键的发育期 易受荷尔蒙和行为变化的影响， 滥用原子吸收分光光度计 用免疫细胞化学和放射免疫法检测NPY和_-内啡肽的含量， 用于分别定量IR细胞和肽水平。此外，mRNA表达的增长 将确定因子受体。生长因子及其受体的存在， 大脑可能表明在肽调节中起重要作用，因此，在神经内分泌中， 功能和焦虑。最后，神经肽激动剂和拮抗剂将被集中输注， 与生殖和情感行为相关的大脑区域。这一目标将 包括体外和体内实验之间的概念验证。这些研究将 提供有关精神症状的生化方面的关键数据， 雄激素暴露。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sex steroids in the brain regulate reproductive behaviors and have regulatory functions beyond the influence on reproduction. For instance, natural and synthetic androgens can induce psychiatric disorders such as anxiety and depression. Knowledge that androgens can modulate specific cellular substrates such as neuropeptides and growth factors has raised relevant questions regarding the cellular mechanisms responsible for the observed behavioral changes under physiological or abused concentrations. Neuropeptides have been associated with reproductive and anxiety-related behaviors. NPY and opioids, are highly expressed in brain regions that mediate reproductive behaviors and anxiety, but also they have been shown to be under hormonal control. However, the cellular events implied in these behaviors are poorly understood and have been addressed mainly in vivo. This proposal studies the biochemical basis underlying reproductive and anxietyrelated behaviors using an in vitro system. Isolated cells from the medial preoptic area and amygdala complex, will be exposed to testosterone and the anabolic androgenic steroid (AAS), 17¿-methyltestosterone. Cultured cells will be isolated from peripubertal rats, since puberty is a critical developmental period susceptible to hormonal and behavioral changes, and for the alarming increase in adolescents misusing AAS. Immunocytochemistry and radioimmunoassay for NPY and _-endorphin will be used to quantify IR-cells and peptide levels, respectively. Also, mRNA expression for growth factor receptors will be determined. The presence of growth factors and their receptors in the brain might suggest an important role in peptide regulation and therefore, in neuroendocrine function and anxiety. Finally, neuropeptide agonist and antagonists will be centrally infused in vivo to brain regions associated with reproductive and affective behaviors. This aim will encompass a proof of concept between the in vitro and in vivo experiments. These studies will provide critical data regarding the biochemical aspects of psychiatric symptoms associated with androgen exposure.