Steroid-Catecholamine Interactions and Behavior

描述（由申请人提供）：本研究的目的是阐明介导日本鹌鹑（Coturnix japonica）食欲和完成雄性性行为激活的神经递质、激素和脑功能之间的基本关系。特别是儿茶酚胺，多巴胺（DA），和睾酮（T）代谢酶，芳香化酶，在男性行为的T激活所发挥的作用将被研究。拟议的工作包括12个实验，5个目标和利用有关鹌鹑性行为的神经内分泌控制的研究结果，使这个物种成为这些研究的独特模型。目的研究视前区芳香化酶细胞向中脑中央灰质的特异性投射，探讨控制性行为表达的神经回路。我们将分析GCt（实验1）中产生的雌激素的行为效应以及该投射组织中可能的性别差异（实验2）。目的2通过分析中枢注射DA能药物的行为效应，探讨DA在性行为控制中的作用（实验3）。目的3将通过研究雌激素受体（ER α和ER β）或类固醇受体辅激活因子-1（SRC-1）表达的性别差异（实验4），并通过反义技术分析SRC-1的功能意义（实验5-6），关注T控制雄性行为和芳香化酶活性（AA）表达的基因组机制。目的4集中于由磷酸化介导的AA的快速变化，并分析了由磷酸化引起的芳香化抑制的可逆性（实验7）和兴奋性氨基酸对AA快速变化控制的贡献（实验8）。AIM 5将通过测量芳香化酶细胞组中存在的17 β雌二醇（E2）水平（实验9），测试E2是否快速影响男性性行为的表达（实验10）以及研究暴露于E2后CREB或酪氨酸羟化酶磷酸化和酪氨酸羟化酶活性的快速变化（实验11-12）。这些研究将提供关于类固醇作用和DA能传递在性行为激活中的相互作用的新信息，从而深入了解男性性功能障碍和性分化或类固醇依赖性疾病的病因。

DESCRIPTION (provided by applicant): The goal of this research is to elucidate fundamental relationships among neurotransmitters, hormones, and brain function mediating the activation of appetitive and consummatory male sexual behavior in Japanese quail (Coturnix japonica). In particular the roles played by the catecholamine, dopamine (DA), and the testosterone (T) metabolizing enzyme, aromatase, in relation to the activation by T of male behaviors will be studied. The proposed work includes 12 experiments in 5 aims and capitalizes on findings concerning the neuroendocrine control of sexual behavior in quail that make this species a unique model for these studies. AIM I concerns the neural circuitry that controls the expression of sexual behavior and focuses on the specific projection of preoptic aromatase cells to the mesencephalic central gray (GCt). We will analyze the behavioral effects of estrogens produced in GCt (Exp 1) and a possible sex difference in the organization of this projection (Exp 2). AIM 2 will investigate the role of DA in the control of sexual behavior by analyzing the behavioral effects of central injections of DAergic drugs (Exp 3). AIM 3 will focus on the genomic mechanisms through which T controls the expression of male behavior and of aromatase activity (AA) by investigating sex differences in the expression of estrogen receptors (ERalpha and ERbeta) or of the steroid receptor coactivator-1 (SRC-1) (Exp 4) and analyzing the functional significance of SRC-1 by antisense techniques (Exp 5-6). AIM 4 focuses on rapid changes in AA mediated by phosphorylations and analyzes the reversibility of the aromatae inhibition by phosphorylations (Exp 7) and the contribution of excitatory amino acids to the control of rapid changes in AA (Exp 8). AIM 5 will investigate the effects of rapid variations in estrogen bioavailability due to fast changes in AA by -measuring the levels of 17beta estradiol (E2) present in aromatase cell groups (Exp 9), testing whether E2 rapidly affects the expression of male sexual behavior (Exp 10) as well as investigating rapid changes in the phosphorylation of CREB or tyrosine hydroxylase and tyrosine hydroxylase activity following exposure to E2 (Exp 11-12). These studies will provide new information about the interplay between steroid action and DAergic transmission in the activation of sexual behavior and thereby provide insight into the etiology of male sexual dysfunction and of sexually differentiated or steroid-dependent diseases.