ANDROGEN REGULATION OF NEUROMUSCULAR FUNCTION

我们的目标是了解细胞和分子机制 负责中枢神经系统的性别分化。 本 该提案探讨了男性化的外周肌肉的贡献， 和神经肌肉接头-这个过程。 我们的实验系统是 非洲爪蟾的喉肌，一种两性异形动物， 雄激素靶向肌受性二形性的雄激素靶向肌支配 运动神经元 我们已经确定， 成年人的肌纤维数量是由于雄激素诱导的肌肉发生 在有限的发展时期。 建议的目标 实验的目的是确定这一过程的细胞基础，阐明 雄激素类固醇的作用和作用部位，并确定是否 男性化的过程包括性别的分化， 神经肌肉接头 我们将研究成肌细胞的诱导，存活和分化， 体内和体外的雄性和雌性发育。 雄激素受体 将使用结合测定和类固醇激素测定来测量表达。 放射自显影 细胞类型将通过电子显微照片进行鉴定 并通过抗体和原位杂交标记。 的作用 成肌细胞性分化中的神经支配将通过阻断 肌肉活动和神经节。 我们将描述 突触神经支配的形态学和检查 乙酰胆碱受体分布 我们相信运动神经元的性分化是受调节的， 至少部分是由于外围的男性化。 雄激素可以 通过获得某些物质来影响性二态的发展 关键的发育过程--细胞特化，存活， 分化和细胞与细胞接触。 我们计划确定 类固醇激素发挥这些作用，为什么有些是有限的， 关键发展阶段或“关键”时期。 这些问题是关键， 揭示大脑如何发育以及神经和内分泌的差异 这是导致男性更容易受到发展的影响的基础， 异常包括一些神经肌肉疾病，失语症和情感障碍 紊乱

Our goal is an understanding of the cellular and molecular mechanisms responsible for central nervous system sexual differentiation. The present proposal explores the contribution of the masculinized periphery - muscle and neuromuscular junction - to this process. Our experimental system is the laryngeal muscle of Xenopus laevis, a sexually dimorphic, androgen-target muscle innervated by sexually dimorphic, androgen-target motor neurons. We have established that the marked sex difference in muscle fiber number of the adult is due to androgen-induced myogenesis during a limited developmental period. The goal of the proposed experiments is to determine the cellular basis of this process, clarify the role and site of action of androgenic steroids and determine whether the process of masculinization includes sexual differentiation of the neuromuscular junction. We will examine myoblast induction, survival and differentiation during male and female development in vivo and in vitro. Androgen receptor expression will be measured using binding assays and steroid autoradiography. Cell types will be identified from electron micrographs and by antibody and in situ hybridization labeling. The role of innervation in myoblast sexual differentiation will be studied by blocking muscle activity and by nerve section. We will characterize the development of synaptic innervation in males and females morphologically and examine acetylcholine receptor distribution. We believe that the sexual differentiation of motor neurons is regulated, at least in part, by masculinization of the periphery. Androgens can effect the development of sexual dimorphisms by gaining access to certain key developmental processes -- cell specification, survival, differentiation, and cell to cell contacts. We plan to determine how steroid hormones exert these effects and why some are limited to certain key developmental stages or "critical" periods. These questions are key to unravelling how the brain develops and the neural and endocrine differences that underlie the increased vulnerability of males to developmental abnormalities including some neuromuscular diseases, aphasias and affective disorders.