Revival of autochthonous adrenocortical stem cells in autoimmune Addison's disease

自身免疫性阿狄森氏病中原位肾上腺皮质干细胞的复兴

• 批准号: G0900001/1
• 负责人: Simon Pearce
• 金额: $ 36.61万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900001%2F1
• 关键词: Revival; autochthonous; adrenocortical; stem; cells

The cortex of the adrenal gland manufactures two steroid hormones, cortisol and aldosterone, that are essential for life. The activity of the adrenal cortex, including cortisol and aldosterone production, is controlled by a master regulatory hormone known as ACTH (adrenocorticotrophic hormone). Too much ACTH causes the adrenal glands to expand and to make too much cortisol. In contrast, too little ACTH causes the adrenals to shrink, and results in serious illness owing to steroid deficiency. All the cells of the adrenal cortex start life by dividing from their parent stem cells which are located around the outer edge of the adrenal gland. The proliferation and growth of these parent stem cells is also strongly regulated by the same hormone, ACTH. Untreated, autoimmune Addison?s disease is an invariably fatal condition. The adrenal cortex becomes destroyed by an immune system attack, leading to deficiency of the vital steroid hormones, cortisol and aldosterone. During the development of Addison?s disease, the body senses the steroid hormone deficiency, so blood ACTH levels become very high (typically 20-times higher than normal). This is an attempt by the body to stimulate the adrenal cells to divide and make more of the essential steroid hormones. However, once diagnosed and treated with replacement steroid tablets, the ACTH levels fall. Critically, this leads to a worsening of the function of any remaining adrenal stem cells and further reduction in functioning adrenal tissue. The idea of the current project is to give back ACTH to people with treated autoimmune Addison?s disease in order to stimulate the stem cells in their adrenal glands back into activity. The treatment with ACTH would initially be by daily injection for 10 weeks. This could ultimately lead to recovery of adrenal gland function and people with Addison?s disease may then be able to stop their steroid medications. Their condition could be cured.

肾上腺皮质制造两种类固醇激素，皮质醇和醛固酮，这是生命所必需的。肾上腺皮质的活动，包括皮质醇和醛固酮的产生，是由一个主调节激素称为ACTH（促肾上腺皮质激素）控制。过多的ACTH会导致肾上腺扩张并产生过多的皮质醇。相反，太少的促肾上腺皮质激素会导致肾上腺萎缩，并导致严重的疾病，由于类固醇缺乏。肾上腺皮质的所有细胞都是通过从位于肾上腺外缘的母体干细胞分裂而开始生命的。这些亲本干细胞的增殖和生长也受到同一种激素ACTH的强烈调节。未经治疗的自身免疫性艾迪森这种病总是致命的。肾上腺皮质被免疫系统攻击破坏，导致重要的类固醇激素、皮质醇和醛固酮缺乏。在艾迪生的发展过程中？当患有这种疾病时，身体感觉到类固醇激素缺乏，所以血液中的ACTH水平变得非常高（通常是正常水平的20倍）。这是身体试图刺激肾上腺细胞分裂并产生更多必需的类固醇激素。然而，一旦诊断和治疗与替代类固醇片剂，ACTH水平下降。重要的是，这会导致任何剩余的肾上腺干细胞的功能恶化，并进一步减少功能性肾上腺组织。目前的项目的想法是给回促肾上腺皮质激素的人与治疗自身免疫性艾迪生？为了刺激他们肾上腺中的干细胞重新活跃起来，ACTH治疗最初是每天注射10周。这可能最终导致肾上腺功能的恢复和艾迪生？的疾病，然后可能能够停止他们的类固醇药物。他们的病是可以治好的。