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

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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.