CELLULAR AND MOLECULAR CHANGES ASSOCIATED WITH REPRODUCTIVE HEALTH

与生殖健康相关的细胞和分子变化

• 批准号: 7720870
• 负责人: Jennifer Luz Barreto Estrada
• 金额: $ 15.3万
• 依托单位: UNIVERSITY OF PUERTO RICO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720870
• 关键词: Address; Adolescent; Affective; Agonist; Amygdaloid structure; Anabolic steroids; Androgen Analogues; Androgens; Anxiety; Behavior; Behavioral; Biochemical; Brain; Brain region; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Cultured Cells; Data; Development; Endorphins; Event; Funding; Gonadal Steroid Hormones; Grant; Growth Factor; Growth Factor Receptors; Hormonal; In Vitro; Institution; Knowledge; Medial; Mediating; Mental Depression; Mental disorders; Methyltestosterone; Molecular; Neuropeptides; Neurosecretory Systems; Opioid; Peptides; Physiological; Preoptic Areas; Puberty; Radioimmunoassay; Rattus; Regulation; Reproduction; Reproductive Behavior; Reproductive Health; Research; Research Personnel; Resources; Role; Source; Symptoms; System; Testosterone; United States National Institutes of Health; base; concept; immunocytochemistry; in vivo; mRNA Expression; receptor; reproductive; research study

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 大脑中的性类固醇调节生殖行为并具有调节功能 超出了对繁殖的影响。例如，天然和合成的雄激素可以 诱发焦虑、抑郁等精神疾病。雄激素可以 调节特定的细胞底物，如神经肽和生长因子 有关导致观察到的行为的细胞机制的相关问题 在生理或滥用浓度下发生变化。神经肽已被关联 与生殖和焦虑相关的行为。 NPY 和阿片类药物在 介导生殖行为和焦虑的大脑区域，而且它们也被 显示处于荷尔蒙控制之下。然而，这些行为中隐含的细胞事件 人们对这些问题知之甚少，并且主要在体内得到解决。本提案研究了 使用体外实验研究生殖和焦虑相关行为的生化基础 系统。来自内侧视前区和杏仁核复合体的分离细胞将暴露于 睾酮和合成代谢雄激素类固醇 (AAS)、17¿-甲基睾酮。 有文化的 细胞将从青春期前后的大鼠中分离出来，因为青春期是一个关键的发育时期 容易受到荷尔蒙和行为变化的影响，并且青少年人数的惊人增加 滥用 AAS。 NPY 和 _-内啡肽的免疫细胞化学和放射免疫分析将 分别用于量化 IR 细胞和肽水平。此外，促进生长的 mRNA 表达 因子受体将被确定。生长因子及其受体的存在 大脑可能在肽调节中发挥重要作用，因此在神经内分泌中也发挥着重要作用 功能和焦虑。最后，神经肽激动剂和拮抗剂将被集中注入 体内与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证明。这些研究将 提供有关精神症状相关生化方面的关键数据 与雄激素暴露。