Androgen and Progesterone Actions on Catecholaminergic Neurons: In vivo study

雄激素和孕酮对儿茶酚胺能神经元的作用：体内研究

• 批准号: 8622433
• 负责人: LYDIA A ARBOGAST
• 金额: $ 7.38万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-18 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8622433
• 关键词: Adult; Anabolism; Androgen Receptor; Androgens; Area; Binding; Blood Circulation; Brain; Brain Stem; Brain region; Catecholamines; Cells; Complex; Confocal Microscopy; Contraceptive Agents; Contraceptive Usage; DNA; Data; Disease; Dopamine; Enzymes; Exhibits; Female; Functional disorder; Gene Expression; Genetic Transcription; Goals; Hormonal; Hormone replacement therapy; Hormones; Hypoactive Sexual Desire Disorder; Hypothalamic structure; In Situ Hybridization; Intervention; Knowledge; Label; Laboratories; Lactation; Learning; Mammals; Maps; Memory; Menstrual cycle; Mental Health; Messenger RNA; Metabolic Diseases; Midbrain structure; Molecular; Movement; Neurons; Neurosecretory Systems; Neurotransmitters; Norepinephrine; Ovarian; Physiological; Physiology; Play; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Maintenance; Progesterone; Progesterone Receptors; Progestins; Protein Isoforms; Psychological reinforcement; Rattus; Regulation; Relative (related person); Reproduction; Rewards; Role; Sleep Wake Cycle; Stanolone; Steroids; Techniques; Testosterone; Time; Transactivation; Tyrosine 3-Monooxygenase; Western Blotting; Women' s Health; base; hormone regulation; in vivo; in vivo Model; mRNA Expression; male; mind control; promoter; public health relevance; receptor; reproductive; reproductive function; reproductive hormone; research study; steroid hormone; steroid hormone receptor

Project Summary/ Abstract The long-term objective of these studies is to understand interactions between androgens and progestins in regulating catecholaminergic neurons. Circulating androgen levels are low in females, but change during the reproductive cycle and play important physiological roles. Progesterone has important functions during the reproductive cycle and is essential in pregnancy maintenance in mammals. Females can exhibit elevated androgen levels in reproductive and metabolic disorders, such as polycystic ovary syndrome. Some of the most commonly used hormonal contraceptives contain progestin compounds, which also exhibit androgenic activities. Thus, there may be times when androgens and progesterone are circulating together at levels sufficient to activate their respective receptors at the same time. Our laboratory has identified a unique interaction of testosterone-bound androgen receptor (AR) and progesterone-bound progesterone receptor (PR) within a steroid responsive region of the tyrosine hydroxylase (TH) promoter. TH is the rate-limiting enzyme in dopamine and norepinephrine biosynthesis. The overall objective of this study is to put molecular interactions of androgens and progesterone into a physiological context in the regulation of TH gene expression. We propose to examine AR and PR effects on TH gene expression in the brains of female rats. The hypothesis for this study is that subpopulations of catecholaminergic neurons express both AR and PR in the same cell and that progesterone and androgens interact to augment TH mRNA expression is brain regions with AR and PR co-localization. Aim 1 is to evaluate the localization of AR and PR in catecholaminergic neuronal groups in the hypothalamus, midbrain and brainstem. Immunohistochemical techniques will be used to identify discrete dopamine and norepinephrine subpopulations, which express AR and PR in the same cells. PR exists in two isoforms, PRA and PRB. Western blot analysis will be used to examine relative expression of PR isoforms in specific brain areas containing catecholaminergic neurons. Aim 2 is to assess interactions between progesterone and dihydrotestosterone (DHT) on TH mRNA levels in specific catecholaminergic neuronal groups. An in situ hybridization technique will be used to examine androgen and progesterone interactions to regulate TH gene expression in AR- and PR-containing catecholaminergic neurons. These studies will enhance our understanding of female reproductive functions and may have implications in non-reproductive functions modulated by catecholamine input. An increased understanding of the mechanism(s) involved in the interactions of these hormones can contribute to better health for women.

项目总结/摘要 这些研究的长期目标是了解雄激素和孕激素之间的相互作用， 调节儿茶酚胺能神经元。女性的循环雄激素水平较低，但在妊娠期间会发生变化。 生殖周期和发挥重要的生理作用。预后在治疗过程中起着重要的作用。 在哺乳动物的生殖周期中是维持妊娠的关键。女性可以表现出 生殖和代谢紊乱中的雄激素水平，如多囊卵巢综合征。一些 大多数常用的激素避孕药含有孕酮化合物， 活动因此，有时候雄激素和孕酮一起循环， 足以同时激活它们各自的受体。我们的实验室发现了一种独特的 睾酮结合雄激素受体（AR）和孕酮结合孕激素受体（PR）相互作用 在酪氨酸羟化酶（TH）启动子的类固醇反应区内。TH是一种限速酶， 多巴胺和去甲肾上腺素的生物合成。本研究的总体目标是将分子相互作用 雄激素和孕激素进入生理背景下的调节TH基因的表达。我们 拟研究雌鼠脑内AR和PR对TH基因表达的影响。假设为 这项研究表明，儿茶酚胺能神经元的亚群在同一细胞中同时表达AR和PR， 孕激素和雄激素相互作用增加TH mRNA表达是AR和PR脑区 共定位目的：1.研究肾上腺皮质激素受体（AR）和孕激素受体（PR）在大鼠海马儿茶酚胺能神经元中的定位， 下丘脑、中脑和脑干。免疫组织化学技术将用于识别离散的 多巴胺和去甲肾上腺素亚群，它们在同一细胞中表达AR和PR。PR存在于两个 同种型，PRA和PRB。蛋白质印迹分析将用于检查PR亚型的相对表达， 含有儿茶酚胺能神经元的特定脑区。目标2是评估 孕酮和双氢睾酮对特异性儿茶酚胺能神经元TH mRNA水平的影响 组原位杂交技术将用于检测雄激素和孕酮的相互作用， 调节含AR和PR的儿茶酚胺能神经元中TH基因的表达。这些研究将 增强我们对女性生殖功能的理解，并可能对非生殖功能产生影响。 由儿茶酚胺输入调节的功能。加深对环境影响所涉机制的了解， 这些激素的相互作用有助于改善妇女的健康状况。