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。现在 提案探讨了男性化的外周肌肉的贡献 和神经肌肉连接--这一过程。我们的实验系统是 非洲爪哇的喉部肌肉是一种两性异形体， 雄激素靶肌肉受性二态、雄激素靶支配 运动神经元。我们已经确定了显著的性别差异 成体肌纤维数量与雄激素诱导的肌发生有关 在有限的发育期。建议的目标是 实验是为了确定这一过程的细胞基础，阐明 雄激素的作用和作用部位，并确定是否 男性化过程包括男性和女性的性别分化 神经肌肉接头。 我们将研究成肌细胞的诱导、存活和分化 雄性和雌性在体内和体外发育。雄激素受体 将使用结合分析和类固醇来测量表达 放射自显影。细胞类型将从电子显微镜照片中识别出来 并通过抗体和原位杂交标记。的作用 成肌细胞性别分化中的神经支配将通过阻断来研究 肌肉活动和神经节段。我们将描述这一发展的特点 男性和女性突触神经支配的形态和观察 乙酰胆碱受体分布。 我们认为运动神经元的性别分化是受调控的， 至少在一定程度上，是通过外围国家的男性化。雄激素可以 通过获得某些特定的基因来影响性别二型性的发展 关键发育过程--细胞规格、存活、 分化，以及细胞与细胞的接触。我们计划确定如何 类固醇激素发挥这些作用，以及为什么某些激素仅限于某些 关键发展阶段或“关键”时期。这些问题是 揭示大脑是如何发育的以及神经和内分泌的差异 这是男性对发育迟缓易感性增加的基础 异常包括一些神经肌肉疾病、失语症和情感性 精神错乱。

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.