THE ROLE OF THE SERTOLI CELL IN SPERMATOGENESIS

支持细胞在精子发生中的作用

• 批准号: 3313554
• 负责人: MARTIN DYM
• 金额: $ 17.69万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3313554
• 关键词: G protein; Leydig cells; Sertoli cells; adenylate cyclase; androgen binding protein; aromatase; cell cell interaction; cell differentiation; cyclic AMP; electron microscopy; follicle stimulating hormone; gene expression; germ cells; hormone receptor; hormone regulation /control mechanism; in situ hybridization; laboratory rat; mixed tissue /cell culture; muscle cells; northern blottings; protein biosynthesis; protooncogene; radioimmunoassay; secretion; sperm; spermatogenesis; testis; testosterone; transferrin

Spermatogenesis is a complex process of differentiation that is clearly dependent upon paracrine interactions among the cellular elements in the testis. The different cells (myoid, germ, Leydig, Sertoli) certainly do not function in isolation, but there is a coordinated combination of events that collectively permit spermatogenesis. Our long term objective is to achieve a better understanding of the factors controlling germ cell differentiation. Our research will emphasize the role of the Sertoli cell in the spermatogenic process and the interdependence of the cellular elements within the testis. During the previous granting period, we developed a novel dual compartment (bicameral) culture system which mimics more closely cells growing in vivo. In this renewal application, we will continue our experiments to characterize the Sertoli cells in bicameral culture and, in particular, attempt to prove that Sertoli cells growing in this culture chamber are more physiological than cells in conventional culture. The effects of other testicular cells on Sertoli cell differentiation will be determined. We have recently demonstrated that the Sertoli cells produce a mitogenic protein which modulates Leydig cell division. We will attempt to determine whether this factor plays a direct role in germ cell mitoses and differentiation. Our recent work demonstrated that pachytene spermatocytes produce a factor(s) which stimulates novel protein secretion by Sertoli cells. We intend to continue our studies on the reciprocal relationship between germ cells and Sertoli cells. The bicameral cell culture chamber has lcd to many novel experiments in the testis, including the ability to recombine simultaneously the cellular elements of the testis in culture in a manner which is analogous to their position in vivo. Sertoli cells will be grown on top of extracellular matrix-coated Millipore filters; myoid cells will be placed on the undersurface of the filters; Leydig cells will be cultured in the basal chamber; different classes of germ cells will be placed on top of the filter with the Sertoli cells. With these experiments we may be able to achieve a greater degree of germ cell differentiation in culture than has been previously possible, especially because of the newly developed bicameral culture chamber. The experiments outlined in this proposal should provide new data on the basic biology of the Sertoli cell and its role in spermatogenesis and on the interdependence of the cellular elements in the testis. This approach could well have significance in the development of future male contraceptives.

精子发生是一个复杂的分化过程 明确取决于细胞元素之间的旁分泌相互作用 在睾丸中。 不同的细胞（Myoid，Germ，Leydig，Sertoli） 当然不孤立地运作，但是有一个协调 共同允许精子发生的事件的组合。 我们的漫长 术语目标是更好地理解因素 控制生殖细胞分化。 我们的研究将强调 Sertoli细胞在精子过程中的作用和 睾丸内细胞元素的相互依赖性。 在 以前的授予期，我们开发了一个新颖的双隔间 （双色）培养系统，该系统模拟更亲密的细胞生长 体内。 在此续订应用程序中，我们将继续实验 表征双色层培养中的Sertoli细胞，尤其是 试图证明该培养室中生长的Sertoli细胞是 在常规培养中比细胞更生理。 效果 Sertoli细胞分化的其他睾丸细胞将是 决定。 我们最近证明了Sertoli细胞会产生 一种调节leydig细胞分裂的有丝分裂蛋白。 我们将 尝试确定该因素是否在生殖细胞中起着直接作用 有丝分裂和分化。 我们最近的工作证明了pachytene 精子细胞产生刺激新蛋白的因子 Sertoli细胞分泌。 我们打算继续学习 生殖细胞与Sertoli细胞之间的相互关系。 这 双层细胞培养室具有LCD，用于许多新型实验 睾丸，包括同时重组细胞的能力 睾丸在培养中的元素以类似于其的方式 体内位置。 Sertoli细胞将在细胞外生长 矩阵涂层的米利波尔过滤器；将肌动物细胞放在 过滤器的地面； leydig细胞将在基础上培养 室；不同类别的生殖细胞将放在 用Sertoli细胞过滤。 通过这些实验，我们可能能够 在培养中获得更大程度的生殖细胞分化，而不是 以前有可能，尤其是因为新开发 两种培养室。 该提案中概述的实验 应提供有关Sertoli细胞及其基本生物学的新数据 在精子发生和细胞的相互依赖性中的作用 睾丸中的元素。 这种方法很可能具有重要意义 未来男性避孕药的发展。