The effects of growth hormone on the ventromedial nucleus of the hypothalamus during food restriction

Abstract

Growth hormone (GH) is a polypeptide hormone secreted by the somatotrophic cells of the anterior pituitary gland. GH secretion occurs in a pulsatile manner and it is stimulated by the stomach-secreted hormone ghrelin and by the GH releasing hormone (GHRH) from the arcuate nucleus, while its inhibition is caused by the somatostatin from the paraventricular nuclei. Beside this, the nutritional state, intense physical activities, stress and fasting are also potential regulators of its release. Peripherally, GH induces tissue growth, cellular protein synthesis, gastrointestinal absorption, increases the synthesis and release of insulin, besides other actions. There are also evidence about the importance of the GH controlling the appetite, sleep, cognition, memory and humor. Recently our group mapped in detail the presence of GH responsive cells in the mouse central nervous system. Among other areas, we found a large amount of GH responsive cells in the ventromedial nucleus of the hypothalamus (VMH), an important region for controlling metabolism, feeding behavior and the counterregulatory responses to hypoglycemia. In this project, we aim to study the metabolic effects caused of GH receptor (GHR) deletion in VMH neurons. Specifically, we will study the consequences during food restriction, which is a situation of high GH secretion. For this purpose, we will use mouse models with conditional deletion of GHR and we will analyze the deficiency effects upon metabolic aspects and behaviors. (AU)