Endocrine Abstracts

Body composition is a major determinant of fitness and health. Many of the problems of aging are caused by detrimental changes in body composition. Hormones play a central role in the regulation of body composition. Our laboratory has been investigating the metabolic and molecular mechanisms of GH action and its interaction with sex steroids in the regulation body composition in adult human. The liver is an important site of physiological interaction as it is a sex steroid responsive organ and a major target of GH action. Oestrogen, when administered orally impairs the GH-regulated endocrine and metabolic function of the liver via a first pass effect. It reduces circulating IGF-I, fat oxidation and protein synthesis, contributing to a loss of lean and a gain of fat mass. Studies in hypopituitary men indicate that testosterone enhances the metabolic effects of GH. Testosterone alone stimulates whole body fat oxidation and protein synthesis, both of which are enhanced by GH. Androgens stimulate extra-hepatic rather than hepatic fat oxidation and enhances protein synthesis independent of IGF-I mediation. In summary, oestrogens and androgens exert divergent effects on the action of GH. The results have therapeutic application for the management of hypopituitarism. Oestrogens should be administered by a parenteral route in women and testosterone be replaced in men to optimize the benefits of GH replacement. The metabolic consequences of long-term treatment of women with oral oestrogen compounds including selective oestrogen receptor modulators are largely unknown and warrant study. In vitro studies show that oestrogen directly attenuate GH action by suppressing GHR function. The GHR signals through the JAK/STAT pathway, which is negatively regulated by SOCS proteins. Our studies reveal that oestrogens inhibit GH signalling by increasing SOCS2 expression. This is a novel paradigm of steroid hormone regulation of cytokine receptor function.