Central effects of growth hormone on energetic metabolism and glicemic control

Abstract

Growth Hormone (GH) is a key anabolic hormone and its action on periferic tissues is related to several biologic functions such as somatic growth, metabolism and cellular processes (cellular division and regeneration). Growth Hormone-Releasing factor (GHRH) and growth hormone-inhibiting hormone (somatostatin), as well as free-fat acids, leptin, ghrelin and neuropeptide Y are important factors that control GH releasing. Nutritional state, intense physical activity, stress and fasting are also powerful releasing factors. There is evidence, but still poorly investigated, that GH might exert effects on the Central Nervous System (CNS), possibly controlling appetite, cognition, memory, mood, sleep, neuronal protection and well-being. Recently, our group mapped in detail the presence of GH responsive cells in the mouse CNS, and identified several brain sites in which GH possibly interacts with leptin, suggesting a direct action on neurons involved in energy balance and glycemia regulation. The aim of the present study is to investigate in detail the GH function in CNS, especially on glycemic control and energetic metabolism at basal situations, as well as during situations in which GH is highly secreted (e.g., food restriction, hypoglycemia and physical activity). For this purpose, we will use mouse models with conditional deletion of GH receptor (GHR-flox mice) in the CNS (Nestin-Cre mice), ventromedial nucleus of hypothalamus and (SF1-Cre mice) or leptin receptor-expressing cells (LepR-Cre mice). (AU)