DEVELOPMENTAL CONTROL OF LEYDIG CELLS BY MIS

目前关于研究荷尔蒙调节的建议 出生后间质细胞的发育整合了李博士长期以来的兴趣 在性别分化和性腺决定方面以及她的研究努力 阐明苗勒氏抑制物质在发育中的作用 睾丸。这项工作与李博士理解的长期目标有关 睾丸测定与成熟鉴定的规律 管理患有双性障碍儿童的新方法。这个 这笔资金将使李博士能够专注于她的科学研究 发展，并集中精力实现这项提案的目标。这个 将投入更多的专门研究时间来获取专业知识 与她密切合作，了解不熟悉的方法(即流式细胞术) 合作者，并扩大了她对快速发展的科学知识的了解 与该项目相关的领域，如细胞周期调控。 广泛的科学交流机会在以下几个会议上提供 麻省理工学院和哈佛大学的系列研讨会和会议致力于 生殖生物学或细胞生物学以及国家科学会议。 心肌梗死是生长和分化因子中转化生长因子-β家族的成员， 导致男性胚胎有性发育过程中的苗勒管内陷 差异化。意想不到的间质细胞增生表型和 然而，在信息系统基因敲除小鼠中的肿瘤发现了信息系统在 在成熟的睾丸中维持正常的间质细胞补充 调节雄激素的产生。管理信息系统的这些动作可能会有治疗作用 对睾丸疾病患儿处理的启示 发展或功能。这项提议将检验这样一个假设： 心肌梗死抑制间质细胞的自由增殖并调节 类固醇合成酶。这项建议的具体目的是澄清 管理信息系统在间质细胞增殖和类固醇合成调控中的作用 不同成熟期原代间质细胞体外培养的应用 间质细胞再生的体内模型。这些研究将 增加我们对细胞控制的新途径的理解 出生后睾丸的增殖和类固醇生成，并提供见解 探讨睾丸肿瘤发生的机制。 对睾丸发育的影响，这项提议将检验假说 提示MISI对间质细胞增殖和类固醇合成有调节作用。在……里面 一般说来，提案中的实验构思良好，假设 是可测试的。基于她的科学和临床专业知识，李博士 有能力开展本提案中概述的研究。

The current proposal to investigate hormonal modulation of postnatal Leydig cell development integrates Dr. Lee's longstanding interest in sexual differentiation and gonadal determination and her research efforts to clarify a role of Mullerian Inhibiting Substance (MIS) in the developing testis. This work is relevant to Dr. Lee's long-term goals of understanding the regulation of testicular determination and maturation and identifying novel approaches to the management of children with intersex disorders. The funding provided by this grant will enable Dr. Lee to focus on her scientific development and concentrate on pursuing the objectives of this proposal. The increased dedicated research time will be invested in gaining expertise with unfamiliar methodology (i.e., flow cytometry) by working closely with her collaborators and in expanding her knowledge of rapidly advancing scientific areas that are relevant to this project, such as cell cycle regulation. Extensive opportunities for scientific exchange are available at several seminar series and conferences at MGH and Harvard that are devoted to Reproductive or Cell Biology as well as national scientific meetings. MIS a member of the TGF-beta family of growth and differentiation factors, causes involution of the Mullerian ducts during male embryonic sexual differentiation. The unexpected phenotypes of Leydig cell hyperplasia and neoplasia in MIS knockout mice, however, revealed novel roles for MIS in maintaining a normal complement of Leydig cells in the maturing testis and regulating androgen production. These actions of MIS may have therapeutic implications for the management of children with disorders of testicular development or function. This proposal will test the hypothesis that MIS prevents the unrestrained proliferation of Leydig cells and regulates steroidogenic enzymes. The specific aims of this proposal are to elucidate the role of MIS in the regulation of Leydig cell proliferation and steroidogenesis using in vitro cell cultures of primary Leydig cells at different maturational stages and an in vivo model of Leydig cell regeneration. These studies will increase our understanding of a novel pathway for control of cellular proliferation and steroidogenesis in the postnatal testis and provide insights into the pathogenesis of testicular tumorigenesis. effects in testicular development, and this proposal will test the hypotheses that MIS can regulate Leydig cell proliferation and steroidogenesis. In general, the experiments in the proposal are well conceived and the hypotheses are testable. Based on her scientific and clinical expertise, Dr. Lee is competent to carry out the studies outlined in this proposal.