Regulation of melatonin receptor expression by gonadotrophin-releasing hormone (GnRH)

促性腺激素释放激素 (GnRH) 调节褪黑激素受体表达

• 批准号: BB/F020309/1
• 负责人: Jonathan Johnston
• 金额: $ 45.57万
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF020309%2F1
• 关键词: Regulation; melatonin; receptor; expression; gonadotrophin

The hormone melatonin has many important functions in biology, many of which involve the regulation of other hormonal systems. Most of our understanding of melatonin biology comes from studies of adult animals, in which melatonin only acts on a restricted number of tissues throughout the body. However, it is known that more tissues in the body are sensitive to melatonin in foetuses and newborns than in adults. To date, the biological significance of the broader sensitivity to melatonin during development is not known. One way in which we can start to explore these undefined roles of melatonin is to gain a clear understanding of the nature of the processes that underlie these developmental changes. This project will build upon recent studies by the applicant and help us to understand how tissues change their sensitivity to melatonin during development. The applicant has recently published multiple research papers investigating the developmental regulation of melatonin sensitivity in gonadotroph cells of the pituitary gland, which is the best-characterised model for studying the developmental biology of melatonin. Pituitary gonadotroph cells are essential for reproduction function, including pubertal development. We have provided preliminary evidence to suggest that the developmental secretion of a brain-derived chemical, gonadotrophin-releasing hormone (GnRH), is the primary stimulus for decreasing sensitivity to melatonin in gonadotroph cells. Furthermore, the effects of GnRH appear to be mediated by a cellular signalling molecule called Egr-1. The current project will be the first to provide a detailed investigation into the role of GnRH in determining melatonin sensitivity. We will use a range of complementary experimental techniques to manipulate both GnRH and Egr-1 activity and then evaluate the effects of these manipulations on melatonin sensitivity. These techniques will include the use of isolated cells grown in laboratory conditions, in order to minimise the use of animals. The results of this work will have important implications for scientists and the public. On completion of the project, we will have a greater understanding of the biological role of melatonin and, more generally, an insight into developmental changes in hormone-secreting cells. As melatonin is available over-the-counter as a food supplement in some countries, this work will also help us to understand potential health risks of taking melatonin in certain situations e.g. during pregnancy.

褪黑激素在生物学中具有许多重要功能，其中许多涉及其他激素系统的调节。我们对褪黑激素生物学的大部分理解来自对成年动物的研究，其中褪黑激素仅作用于全身有限数量的组织。然而，已知胎儿和新生儿体内更多的组织比成人对褪黑激素敏感。到目前为止，在发育过程中对褪黑激素更广泛的敏感性的生物学意义尚不清楚。我们可以开始探索褪黑激素的这些未定义的角色的一种方法是对这些发育变化背后的过程的本质有一个清晰的理解。该项目将建立在申请人最近的研究基础上，并帮助我们了解组织在发育过程中如何改变对褪黑激素的敏感性。申请人最近发表了多篇研究论文，研究了垂体促性腺激素细胞中褪黑激素敏感性的发育调节，这是研究褪黑激素发育生物学的最佳表征模型。垂体促性腺激素细胞对生殖功能，包括青春期发育至关重要。我们已经提供了初步的证据表明，脑源性化学物质，促性腺激素释放激素（GnRH）的发育分泌，是降低促性腺激素细胞对褪黑激素敏感性的主要刺激。此外，GnRH的作用似乎是由称为Egr-1的细胞信号分子介导的。目前的项目将是第一个提供一个详细的调查GnRH在确定褪黑激素敏感性的作用。我们将使用一系列互补的实验技术来操纵GnRH和Egr-1活性，然后评估这些操作对褪黑激素敏感性的影响。这些技术将包括使用在实验室条件下生长的分离细胞，以尽量减少动物的使用。这项工作的结果将对科学家和公众产生重要影响。在项目完成后，我们将有一个更好的了解褪黑激素的生物学作用，更一般地说，在褪黑激素分泌细胞的发育变化的洞察力。由于褪黑激素在一些国家可作为非处方食品补充剂，这项工作也将帮助我们了解在某些情况下服用褪黑激素的潜在健康风险，例如在怀孕期间。

项目成果

In vitro regulation of melatonin receptor expression by gonadotrophin-releasing hormone (GnRH)

促性腺激素释放激素 (GnRH) 体外调节褪黑激素受体表达

• 作者: Sung-Eun Bae (Co-Author)

In vivo and in vitro regulation of MT1 melatonin receptor expression by gonadotrophin-releasing hormone (GnRH) and early growth response factor-1 (Egr-1)

促性腺激素释放激素 (GnRH) 和早期生长反应因子 1 (Egr-1) 对 MT1 褪黑激素受体表达的体内和体外调节

• 作者: Jonathan Johnston (Co-Author)