ANDROGEN REGULATION OF NEUROMUSCULAR FUNCTION

我们研究计划的目标是了解细胞和 控制神经性别分化的分子事件， 肌肉.在非洲爪蟾中，发声器官的雄性化是 由通过细胞内受体起作用的性腺类固醇控制 proteins.我们正在研究雄激素的分泌 在喉的发育过程中增加肌肉纤维的数量。 我们的目标是发现雄激素何时起作用， 以及如何在雄激素受体蛋白水平非常高， 喉是受调节的。我们将在非常长的时间内测量血清激素水平， 使用放射免疫分析法进行早期发育。雄激素的作用会被阻断 在不同发育阶段和对肌纤维数量的影响 化验。含雄激素受体喉细胞的分布 将在组织培养中研究雄激素受体表达 在单细胞水平上。雄激素对成肌细胞存活的影响， 将在体外测定增殖和融合。雄激素调节 受体在单细胞水平的表达。雄激素对 将在体外测定成肌细胞存活、增殖和融合。 雄激素受体在信使RNA水平的表达调控 将使用北方分析和原位杂交进行检查。 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现型。肌肉和神经是目标 因为它们含有特定的受体蛋白。 与雄激素分泌异常或 受体表达包括假两性畸形，睾丸 女性化、神经内分泌和肌肉异常和改变 在性别认同上。了解雄激素的基本机制 可以从动物模型的研究中获得作用， 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.