The Metabolic Effects of Oestrogens and SERMs: Regulatory interactions with the GH-IGF-system in health and disease

雌激素和 SERM 的代谢作用：与 GH-IGF 系统在健康和疾病中的调节相互作用

• 批准号: nhmrc : 376003
• 负责人: Dr Kin-Chuen Leung
• 金额: $ 25.28万
• 依托单位: Garvan Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/metabolic-effects-oestrogens-health-disease/97210
• 关键词: Metabolic; Effects; Oestrogens; SERMs; Regulatory

This project extends work aimed at understanding how GH and sex hormones work together to optimise physical health in women and men. It addresses the benefits and safety of oestrogen compounds in relation to their effects on body fat and muscle (body composition). Oestrogen compounds are among the most widely used medicines and include tradition oestrogens (female hormone) and synthetic oestrogens called SERMs. Oestrogens are used in young women as oral contraception and in the postmenopause for replacement therapy. Body composition is an important determinant of fitness and health. Obesity reduces fitness and increases the risk of diabetes and heart attacks while muscle loss causes weakness and frailty. GH is a major regulator of body composition; it acts by breaking down fat and building muscle mass. We discovered that oestrogens, when taken as a tablet interferes with the action of GH and causes detrimental changes in body composition. On the positive side, we have exploited the GH blocking action to treat acromegaly. This is a debilitating disease of excessive GH production from a pituitary tumour and for which available drug treatments are very expensive and require injection. The effects of SERMs on body composition are unknown. SERMs are interesting compounds because they act like oestrogens in some but as oestrogen blockers in other tissues. These are widely used in the treatment of breast cancer and osteoporosis. The extent to which they interfere with the action of GH has not been studied. They may exert additional effects because they act on the pituitary gland to reduce the secretion of GH. They may also prove to be effective in acromegaly which could extend their usefulness to men. In summary, the work will provide important information on the long-term benefits of SERMs in patient groups that tend to be frail. It may also prove to be a simple and inexpensive treatment for acromegaly.

该项目扩展了旨在了解生长激素和性激素如何共同作用以优化女性和男性身体健康的工作。它阐述了雌激素化合物对身体脂肪和肌肉(身体成分)的影响的益处和安全性。雌激素化合物是最广泛使用的药物之一，包括传统的雌激素(女性激素)和被称为SERM的合成雌激素。雌激素在年轻女性中用作口服避孕药，在绝经后用作替代疗法。身体成分是健康和健康的重要决定因素。肥胖降低了健康，增加了患糖尿病和心脏病的风险，而肌肉丧失则会导致虚弱。生长激素是身体成分的主要调节器；它通过分解脂肪和建立肌肉群起作用。我们发现，当雌激素作为药片服用时，会干扰生长激素的作用，并导致身体成分的有害变化。从积极的方面来看，我们已经利用生长激素阻断作用来治疗肢端肥大症。这是一种垂体瘤分泌过量生长激素的衰弱疾病，现有的药物治疗非常昂贵，需要注射。SERM对身体成分的影响尚不清楚。SERM是有趣的化合物，因为它们在某些组织中起到雌激素的作用，但在其他组织中起到雌激素阻滞剂的作用。它们被广泛用于乳腺癌和骨质疏松症的治疗。它们在多大程度上干扰生长激素的作用尚未得到研究。它们可能会发挥额外的作用，因为它们作用于脑下垂体，减少生长激素的分泌。它们在肢端肥大症中也可能被证明是有效的，这可能会将它们的用途扩展到男性。总而言之，这项工作将提供关于SERM在倾向于脆弱的患者群体中的长期益处的重要信息。它也可能被证明是治疗肢端肥大症的一种简单而廉价的治疗方法。