MICA: Investigating kisspeptin receptor signalling to improve the treatment of reproductive disease

MICA：研究 Kisspeptin 受体信号传导以改善生殖疾病的治疗

• 批准号: MR/W018934/1
• 负责人: Waljit Dhillo
• 金额: $ 83.13万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW018934%2F1
• 关键词: MICA; Investigating; kisspeptin; receptor; signalling

Kisspeptin is the central controller of reproductive hormone secretion from the hypothalamus. Our group's research has identified a number of reproductive disorders that would benefit from treatment using kisspeptin based therapies. However, there remain many unanswered questions as to how kisspeptin interacts with its receptor. For example, it is known that giving too much kisspeptin can reduce the ability of kisspeptin to induce hormonal stimulation. Additionally, levels of oestrogen at the time of administration can affect the hormonal response to kisspeptin. Moreover, a number of new drugs have been generated that act through the kisspeptin receptor. However, the precise way by which these new kisspeptin based drugs or how oestrogen interacts with the kisspeptin receptor has not been fully described.Therefore, we will conduct research to understand how natural kisspeptins and newly developed drugs that act on the kisspeptin receptor exert their effects inside cells, how this is altered in times of excessive stimulation, and the effect of changes in oestrogen levels on these processes. In this proposal, we have assembled a team of experts from across the globe to conduct cutting edge experiments to better understand signalling at the kisspeptin receptor. We will work with an industry partner to test an oral kisspeptin based drug that is still in development, as well as other recently developed kisspeptin receptor stimulators. We will use an animal model of hypothalamic amenorrhoea (one of the commonest causes of loss of periods and subfertility) to develop a protocol using a kisspeptin-based therapy that can be used to restore reproductive health. In summary, it is essential to better understand the action of kisspeptin and kisspeptin-based drugs at the kisspeptin receptor. This work will enable us to develop treatment protocols using kisspeptin or kisspeptin-like drugs that will improve the care of patients suffering from reproductive disorders.

Kisspeptin 是下丘脑分泌生殖激素的中央控制器。我们小组的研究已经确定了许多生殖疾病，这些疾病可以受益于基于 Kisspeptin 的疗法的治疗。然而，关于 Kisspeptin 如何与其受体相互作用，仍有许多悬而未决的问题。例如，已知给予过多的 Kisspeptin 会降低 Kisspeptin 诱导激素刺激的能力。此外，给药时的雌激素水平会影响对 Kisspeptin 的激素反应。此外，已经产生了许多通过 Kisspeptin 受体起作用的新药物。然而，这些新的 Kisspeptin 药物的精确方式或雌激素如何与 Kisspeptin 受体相互作用的方式尚未得到充分描述。因此，我们将进行研究以了解天然 Kisspeptin 和作用于 Kisspeptin 受体的新开发药物如何在细胞内发挥作用，在过度刺激时细胞内的作用如何改变，以及雌激素水平的变化对这些过程的影响。在这项提案中，我们召集了来自全球各地的专家团队进行前沿实验，以更好地了解 Kisspeptin 受体的信号传导。我们将与行业合作伙伴合作，测试仍在开发中的基于口服 Kisspeptin 的药物，以及其他最近开发的 Kisspeptin 受体刺激剂。我们将使用下丘脑闭经（导致月经丢失和生育力低下的最常见原因之一）的动物模型来开发一种使用基于 Kisspeptin 的疗法的方案，该疗法可用于恢复生殖健康。总之，有必要更好地了解 Kisspeptin 和 Kisspeptin 类药物对 Kisspeptin 受体的作用。这项工作将使我们能够开发使用 Kisspeptin 或 Kisspeptin 类药物的治疗方案，从而改善对患有生殖障碍的患者的护理。