Role of Liver Receptor Homologue-1 (LRH-1) in male germ cells

在历史上，类固醇性激素-雌激素和雄激素-分别被认为是女性和男性特异性的性激素.雌激素由卵巢产生，调节女性特有的过程，如排卵和女性性特征的发育，而雄激素由睾丸产生，调节男性特有的功能。然而，现在很清楚，雌激素和雄激素之间的区别并不明显。例如，我们现在知道雌激素是在睾丸内产生的，在男性生育能力中起着非常重要的作用。不能合成雌激素的男性患者是不育的。同样，不能产生雌激素的小鼠也是不育的，这是由于精子产生缺陷。因此，雌激素对正常男性生育力至关重要，睾丸内雌激素产生减少可能是不孕症的重要原因，这在临床上很容易治疗。蛋白质LRH-1调节其他组织中的雌激素产生。该提案旨在通过鉴定LRH-1调控的基因以及在睾丸中与其相互作用的蛋白质来确定LRH-1在睾丸雌激素产生中的作用。我们还旨在研究不育男性中这些蛋白质的结构。这些研究将确定与男性不育相关的新基因，并可能导致开发更有效的治疗这种常见疾病的方法。

Historically the steroid sex hormones - oestrogens and androgens - have been regarded as female- and male- specific sex hormones, respectively. Oestrogens are produced by the ovary and regulate female-specific processes such as ovulation and development of female sexual characteristics, whereas androgens are produced by the testis and regulate male-specific functions. However it is now clear that the distinction between oestrogen and androgen is not a sharp one. For example, we now know that oestrogens are produced within the testis and play a very important role in male fertility. Human males patients who are unable to synthesise oestrogens are infertile. Similarly, mice that cannot produce oestrogens are also infertile, due to a defect in sperm production. Oestrogens are therefore critical for normal male fertility, and reduced oestrogen production within the testis may be a significant cause of infertility which would be easily treatable in the clinic. The protein LRH-1 regulates oestrogen production in other tissues. This proposal aims to identify the role of LRH-1 in testicular oestrogen production by identifiying the genes regulated by LRH-1 and the proteins that interact with it in the testis. We also aim to study the structure of these proteins in infertile men. These studies will define new genes associated with male infertility and may lead to the development of more effective treatments for this common condition.