Effects of growth hormone on POMC, cholinergic and hypothalamic paraventricular nucleus neurons: implications for energy and glycemic metabolism control

Abstract

The growth hormone (GH) is a pituitary hormone classically responsible for promoting somatic growth and its secretion is regulated by different factors, including nutritional and metabolic signals. GH exerts its effects through its membrane receptor, GHR, culminating in the phosphorylation of STAT5 that acts as a transcription factor regulating the expression of target genes. Studies suggest a possible role of GH in the control of body composition, food intake, insulin sensitivity and glucose tolerance. In addition, our group has recently shown that critical hypothalamic areas in metabolic control are responsive to acute GH stimulation (Furigo et al., 2017); however, the role of GH in these areas is not clarified. Thus, the hypothesis of this project is that the action of GH in certain neuronal populations is crucial in energy and glycemic homeostasis, as well as in the response to certain physiological stress conditions, in which GH is widely secreted. Therefore, our aim is to evaluate the effects of neuronal-specific inactivation of GHR in neuronal populations that regulate the energy and glycemic metabolism. To do so, we will use animal models of the Cre-lox system for the ablation of GHR in POMC neurons, cholinergic neurons (including those that regulate the parasympathetic nervous system) and the paraventricular nucleus of the hypothalamus. We intend to evaluate of energy and glycemic metabolism, as well as the ability to respond to situations of hypoglycemia and food restriction. This study may include the GH as an important factor regulating metabolism, through its action in neuronal populations known to be related to metabolic control.