The Role of FSH in Spermatogenesis

该项目旨在研究FSH和睾酮这两种主要荷尔蒙如何在成年后控制精子的发育和生产。在之前由NHMRC支持的研究中，我们第一个推翻了长期以来的信念，即FSH对所有温血动物精子产生的开始至关重要。这一洞察力是通过使用转基因小鼠品系进行的实验得出的。我们利用这种小鼠品系开发了一种新的实验范式，为激素如何启动和支持精子产生提供了独特的见解。在本提案中，我们希望进一步开展这项研究。尽管我们已经证明FSH对精子产生的启动或持续不是至关重要的，但我们相信它仍然在导致足够多的睾丸支持细胞数量的增长方面发挥重要作用。这些高度专业化的细胞具有支持、滋养和协调精子产生的独特工作。已知支持细胞是FSH体内唯一的靶细胞，因此FSH必须专门作用于支持细胞。我们认为，这几乎只发生在生命早期--从出生前开始，一直到婴儿早期--远远早于第一次产生精子的成年生活。通过这种方式，正在研究的这些过程决定了成熟睾丸的大小。我们研究这两种主要激素如何控制精子产生的新方法包括开发具有额外和独特FSH活性的新型转基因小鼠，以及一些新的研究方法，用于利用基因治疗和细胞移植技术了解FSH如何作用于Sertoli细胞。这项研究有可能发现以前无法解释的男性不育的新原因(大多数到目前为止还没有已知的原因)，帮助开发更好的荷尔蒙男性避孕药，并满足一些不育男性需要昂贵的治疗。

This project aims to study how the two main hormones, FSH and testosterone, control the development and production of sperm throughout adult life. In previous NHMRC-supported research we were the first to overturn the long-standing belief that FSH was vital to the start of sperm production in all warm-blooded animals. This insight was achieved from experiments using a genetically modified strain of mouse. We used this mouse strain to develop a new experimental paradigm to provide unique insight into how hormones start up and support sperm production. In this present proposal we wish to take this research further. Although we have shown that FSH is not vital to the startup or continuing of sperm production, we believe it still does have an important role in causing the growth of a large enough population of Sertoli cells of the testis. These highly specialised cells have the unique job to support, nourish and coordinate the production of sperm. Sertoli cells are known to be the only target in the body for FSH and so that FSH must act upon them exclusively. We believe this occurs almost solely during early life - starting before birth and into early infancy - well before adult life when sperm are produced for the first time. In this way these processes being studied determine the size of mature testis. Our new approaches to studying the question of how the two main hormones control sperm production involve developing new types of genetically modified mice which have extra and exclusive FSH activity as well as some new research methods to be applied to understanding how FSH acts on the Sertoli cell using techniques derived from gene therapy and from cell transplantation. This research has the possibility to uncover new causes of previously unexplained male infertility (the majority having no known cause so far), to help develop better hormonal male contraceptives, and to quetion the need for expensive treatments for some infertile men.