Novel Regulators Of Glucose Metabolism And Inflammation In Adipose Tissue Of Females
Funder
National Health and Medical Research Council
Funding Amount
$282,830.00
Summary
Obesity is a common problem which can lead to development of diabetes and heart disease. One of the major mechanisms by which obesity leads to these diseases involves a defect in the ability of insulin to stimulate uptake of glucose into cells. We have found that excess of the sex hormone testosterone in women can contribute to this defect in tissues. This study will investigate why testosterone causes this defect in females and whether this defect can be prevented using existing drug therapies.
Ageing, Obstructive Sleep Apnea (OSA) and obesity are becoming more common in the community. Each is associated with increased heart disease and metabolic disorders. Understanding how androgen dysregulation exacerbates OSA, obesity and ageing and how androgen treatments alter these conditions may lead to reduced cardiometabolic dysfunction and improved health.
Mechanisms Of Pro-atherogenic Effects Of Androgens In Human Vascular Cells
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Atherosclerosis is the most important cardiovascular disease and is now the leading cause of death in Western societies. A major clue to the causality of the disease is the striking gender gap in its prevalence and severity. The gender gap in atherosclerotic cardiovascular disease may be due to genetic, lifestyle or hormonal differences between males and females. Of these, hormonal differences are the most amenable to therapeutic intervention. Accordingly, there has been a lot of interest in the ....Atherosclerosis is the most important cardiovascular disease and is now the leading cause of death in Western societies. A major clue to the causality of the disease is the striking gender gap in its prevalence and severity. The gender gap in atherosclerotic cardiovascular disease may be due to genetic, lifestyle or hormonal differences between males and females. Of these, hormonal differences are the most amenable to therapeutic intervention. Accordingly, there has been a lot of interest in the potential protective effects of estrogens but few have studied the role of androgens with sophisticated approaches to androgen physiology and pharmacology. Clues from epidemiological and our recent studies suggest that androgenic influences on atherosclerosis may involve positive and negative effects on atherogenesis but the mechanisms are not understood. We now propose a comprehensive approach to studying androgenic effects on vascular biology both to enhance knowledge as well as potentially opening new therapeutic options in selective androgen receptor modulation.Read moreRead less
Regulation Of Growth Hormone Action By Sex Steroids: Metabolic Implications For Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$353,250.00
Summary
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 ....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.Read moreRead less
Oestrogens And The Metabolic Process: Regulatory Interaction With The GH-IGF-system In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Growth hormone (GH) plays a key role in controlling body metabolism, fat and muscle in adult life. The female hormone oestrogen controls how much GH is secreted and how well it acts. Drugs that act like or interfere with the action of oestrogen are used increasing for the treatment of many conditions e.g. growth, cancer and osteoporosis. This proposal examines their impact on cardiovascular and physical health.
The Mechanisms Of The Anabolic Actions Of Androgens In Bone.
Funder
National Health and Medical Research Council
Funding Amount
$470,960.00
Summary
Androgens (male sex hormones) are one of the few agents that increase bone formation. Androgens act by binding to a specific protein, the androgen receptor (AR). To understand exactly how androgens increase bone formation, we will study mice in which the AR is inactivated only in bone forming cells at specific stages of their development. Understanding the way in which androgens act on bone to increase size and strength will be of great benefit in the design of new treatments for osteoporosis.
Androgen Receptor Signalling And Progression Of Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$462,750.00
Summary
Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because pr ....Prostate cancer is a major health problem in Australia, being the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis and treatment of prostate cancer, there are no effective treatments for advanced (metastatic) disease that has spread to other parts of the body. Currently, the only therapy for advanced disease involves the reduction in circulating androgens such as testosterone by surgical or medical castration, i.e. androgen ablation. Because prostate cells are dependent on testicular androgens for their survival, surgical or medical castration results in an initial tumour regression. However, tumours inevitably develop resistance to current forms of androgen ablation therapy. Inappropriate activation of androgen signalling by non-testicular androgens or other agents may stimulate tumour growth following androgen ablation. In this study, we aim to identify and characterise determinants of the specificity and sensitivity of activation of the androgen receptor, which is the primary mediator of androgen action. Current androgen ablation treatments for prostate cancer only target the availability of androgenic ligands. We propose that it is also necessary to target the androgen receptor itself, because it can be activated by ligands other than testicular androgens. Therefore, we will also evaluate a panel ofagents that target different aspects of the androgen signalling axis, combined with androgen ablation using a cyclical approach to prevent or delay disease progression.Read moreRead less