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

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。它解决了雌激素化合物的益处和安全性与其对身体脂肪和肌肉（身体组成）的影响。雌激素化合物是最广泛使用的药物之一，包括传统雌激素（雌性激素）和称为SERM的合成雌激素。雌激素用于年轻妇女口服避孕药和绝经后妇女的替代疗法。身体成分是健康的重要决定因素。肥胖会降低健康水平，增加患糖尿病和心脏病的风险，而肌肉减少会导致虚弱和脆弱。生长激素是身体组成的主要调节剂;它通过分解脂肪和建立肌肉质量来发挥作用。我们发现，雌激素，当作为片剂服用时，会干扰GH的作用，并导致身体成分的有害变化。在积极的一面，我们已经利用生长激素阻断行动，以治疗肢端肥大症。这是一种使人衰弱的疾病，由垂体瘤产生过多的GH，可用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雌激素的作用，但在其他组织中起雌激素阻断剂的作用。这些被广泛用于治疗乳腺癌和骨质疏松症。它们干扰GH作用的程度尚未研究。它们可能会产生额外的影响，因为它们作用于脑垂体，减少GH的分泌。他们也可能被证明是有效的肢端肥大症，这可能会扩大其有用的男性。总之，这项工作将提供有关SERM对身体虚弱的患者群体的长期益处的重要信息。它也可能被证明是一种简单而廉价的治疗肢端肥大症的方法。

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.