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

肝脏受体同源物 1 (LRH-1) 在雄性生殖细胞中的作用

• 批准号: nhmrc : 289318
• 负责人: Dr Colin Clyne
• 金额: $ 14.95万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-liver-receptor-germ-cells/97396
• 关键词: Role; Liver; Receptor; Homologue; LRH

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.

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有的性激素。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，雌激素在睾丸内产生，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，由于精子产生缺陷，不能产生雌激素的老鼠也不能生育。因此，雌激素对正常的男性生育能力至关重要，睾丸内雌激素分泌减少可能是导致不育的重要原因，这在临床上很容易治疗。LRH-1蛋白调节其他组织中雌激素的产生。本研究旨在通过鉴定睾丸中受LRH-1调控的基因及其相互作用的蛋白，来确定LRH-1在睾丸雌激素产生中的作用。我们还旨在研究这些蛋白质在不育男性中的结构。这些研究将确定与男性不育相关的新基因，并可能导致开发出更有效的治疗这种常见疾病的方法。