ANDROGEN REGULATION OF NEUROMUSCULAR FUNCTION

我们研究计划的目标是了解细胞和 控制神经和性分化的分子事件 肌肉。在非洲爪哇，发声器官的男性化是 由细胞内受体作用的性腺类固醇所控制 蛋白质。我们正在研究雄激素是如何分泌的 在发育中的喉部产生更多的肌肉纤维。 我们的目标是发现雄激素何时起作用，细胞类型是什么 以及非常高的雄激素受体蛋白水平如何 喉咙是有规律的。我们将在非常短的时间内测量血清激素水平 使用放射免疫分析进行早期发育。雄激素的作用将被阻断 不同发育阶段对肌纤维数量的影响 化验过了。含雄激素受体的喉细胞的分布 将在组织培养中研究跟随雄激素受体的表达 在单细胞水平上。雄激素对成肌细胞存活的影响 将在体外检测增殖和融合情况。雄激素的调节 受体在单细胞水平的表达。雄激素对血管紧张素转换酶的影响 成肌细胞的存活、增殖和融合将在体外进行检测。 雄激素受体在信使RNA水平的表达调控 将通过Northern分析和原位杂交进行检测。 发育过程中雄激素的分泌控制着 大多数脊椎动物的雄性表型。肌肉和神经是目标 对雄激素的作用，因为它们含有特定的受体蛋白。 与雄激素分泌异常相关的临床疾病或 受体表达包括假两性畸形、睾丸 女性化、神经内分泌和肌肉的异常和改变 在性别认同上。对雄激素基本作用机制的认识 作用可以从动物模型的研究中获得，并且在 了解人类临床疾病的基础。

The goal of our research program is to understand the cellular and molecular events that control sexual differentiation of nerves and muscles. In Xenopus laevis, masculinization of the vocal organ is controlled by gonadal steroids acting through intracellular receptor proteins. We are investigating how secretion of androgenic hormones produces increases in muscle fiber number in developing larynx. Our aims are to discover when androgens act, what cell types are responsible and how the very high androgen receptor protein levels in larynx are regulated. We will measure serum hormone levels during very early development using radioimmunoassay. Androgen action will be blocked at different developmental stages and effects on muscle fiber number assayed. The distribution of androgen receptor containing laryngeal cells will be studied in tissue culture to follow androgen receptor expression at the single cell level. Effects of androgen on myoblast survival, proliferation and fusion will be assayed in vitro. Regulation of androgen receptor expression at the single cell level. Effects of androgen on myoblast survival, proliferation and fusion will be assayed in vitro. Regulation of androgen receptor expression at the messenger RNA level will be examined using Northern analyses and in situ hybridization. Androgen secretion during development controls expression of the masculine phenotype in most vertebrates. Muscles and nerves are targets for androgen action because they contain specific receptor proteins. Clinical disorders associated with abnormalities in androgen secretion or receptor expression include pseudohermaphroditism, testicular feminization, neuroendocrine and muscular abnormalities and alterations in gender identity. An understanding of the basic mechanisms for androgen action can be obtained from studies in animal models and is essential in understanding the basis of human clinical disorders.