Regulation of growth hormone action by sex steroids: metabolic implications for health and disease

健康与否取决于身体成分、体内脂肪和瘦组织的数量。肥胖会增加患糖尿病、高血压和心脏病的风险，而肌肉萎缩会降低力量和体能。身体成分由激素控制，如生长激素(GH)，它通过刺激新陈代谢(燃烧)减少身体脂肪，通过刺激蛋白质合成增加瘦肉组织。生长激素的这些代谢作用是通过肝脏进行的。这项建议旨在了解性激素如何控制女性和男性的身体脂肪和肌肉数量。根据我们实验室以前的研究，我们认为性激素控制生长激素对肝脏的作用。我们将检验这一假设，即雌激素损害肝脏燃烧脂肪和合成蛋白质的能力，以回应生长激素，而男性激素则有相反的作用。只有当雌激素作为片剂服用时，雌激素的作用才会发生，因为肝脏在肠道吸收后暴露在高浓度的这种激素中。它会导致绝经后女性增加脂肪和失去肌肉。除了雌激素，还有许多其他具有雌激素样活性的化合物，如植物雌激素(植物中发现的雌激素)和SERM(用于治疗骨质疏松症)。它们对肝脏和身体成分的影响尚不清楚，但由于它们在社区中的广泛使用而很重要。这些研究的意义在于通过确定雌激素化合物对肝脏的代谢影响来优化其益处。在男性中，了解男性荷尔蒙是如何作为合成代谢介质工作的，可能会带来治疗蛋白质肌肉萎缩的方法。

Fitness and health is determined by body composition, the amount of fat and lean tissue in the body. Obesity increases the risk of diabetes, blood pressure and heart attacks, while muscle wasting reduces strength and fitness. Body composition is controlled by hormones such as growth hormone (GH) which reduces body fat by stimulating its metabolism (burning) and increases lean tissue by stimulating protein synthesis. These metabolic actions of GH are exerted through the liver. This proposal seeks to understand how sex hormones control the amount of body fat and muscle in women and men. Based on previous research in our laboratory, we propose that sex hormones control the action of growth hormone on the liver. We will test the hypothesis that oestrogens impair the ability of the liver to burn fat and build protein in response to GH while male hormones have the opposite effect. The effect of oestrogen occurs only when oestrogen is taken as a tablet because the liver is exposed to high concentrations of this hormone after gut absorption. It causes postmenopausal women to gain fat and lose muscle. Apart from oestrogens, there are many other compounds with oestrogen-like activities such as phytooestrogens (oestrogens found in plants) and SERMs (used for treating osteoporosis). Their effect on the liver and body composition are unknown but important because of their widespread use in the community. The significance of these studies relate to optimising the benefits of oestrogen compounds by defining their metabolic effects on the liver. In men, understanding how male hormones work as anabolic agents may lead to ways of treating protein muscle wasting.