ANDROGEN REGULATION OF NEUROMUSCLAR FUNCTION

雄激素对神经肌肉功能的调节

• 批准号: 2263718
• 负责人: DARCY B KELLEY
• 金额: $ 26.27万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2263718
• 关键词: Xenopus; alternatives to animals in research; androgen receptor; androgens; axon; embryo /fetus; fresh water environment; growth /development; hormone regulation /control mechanism; innervation; larynx muscle; molecular biology; motor neurons; myogenesis; neurogenesis; neuromuscular function; nonmammalian vertebrate embryology; oligonucleotides; polymerase chain reaction; receptor expression; secretion; sex differentiation; thyroxine

Androgen secretion during development controls the expression of masculine sexual behaviors 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 psychosexual 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 for understanding the basis of human endocrine disorders. The goal of this research program is a molecular understanding of how androgenic steroids control sexually differentiation. In particular, this proposal focuses on hormone- directed differentiation of motor neuron and muscle fiber number in a highly androgen-sensitive experimental system, laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. The numbers of vocal motor neurons and target muscle fibers are sexually dimorphic in adults; sex differences are due to the secretion of androgen from the male testes during development. Expression of an intracellular protein, the androgen receptor, in both muscle and motor neurons permits the direct action of androgens. The goal of the proposed studies is to unravel the interactions between these components - androgen secretion and expression of its receptor, developing muscle and its innervation - responsible for sexual differentiation of the vocal system by examining the control of androgen sensitivity, the role of androgen secretion and innervation in the control of laryngeal muscle fiber number and the role of androgen secretion and muscle fiber addition in the control of laryngeal motor neuron number.

发育过程中雄激素的分泌控制着 大多数脊椎动物的雄性性行为。 肌肉和神经 雄激素作用靶点，因为它们含有特异性受体 proteins. 与雄激素异常相关的临床疾病 分泌或受体表达包括假两性畸形， 睾丸女性化、神经内分泌和性心理异常 以及性别认同的改变 了解基本的 雄激素作用的机制可以从动物实验中获得 模型，是了解人体内分泌的基础是必不可少的 紊乱 这个研究项目的目标是 了解雄激素类固醇如何控制性行为 分化 特别是，这项建议侧重于激素- 定向分化运动神经元和肌纤维数量 高度雄激素敏感的实验系统，喉肌和 爪蟾的运动神经元。 声音的数量 运动神经元和靶肌纤维在成年人中具有性二态性; 性别差异是由于雄性睾丸分泌雄激素所致 在发展过程中。 一种细胞内蛋白的表达，雄激素 肌肉和运动神经元中的受体允许的直接作用 雄激素 拟议研究的目标是解开 这些成分之间的相互作用-雄激素分泌和表达 它的受体，发育中的肌肉和它的神经支配-负责 性别分化的声音系统通过检查控制 雄激素敏感性，雄激素分泌和神经支配在 喉肌纤维数量的控制与雄激素的作用 分泌物和肌纤维的添加在喉运动控制中的作用 神经元数目