The importance of growth hormone (GH) action on the dorsomedial nucleus of the hypothalamus

• Grant number: 23/17012-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Jose Donato Junior
• Grantee: Giulianna Moscatelli
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions, AP.TEM

Abstract

Growth hormone (GH) is produced by the anterior pituitary gland and when released into the circulation, it acts on its target tissues. GH secretion is regulated by two hypothalamic hormones: GH-releasing hormone (GHRH) with a stimulating action and somatostatin (SST) with an inhibitory action on GH secretion by the pituitary gland (Hataya et al., 2001). GH has some functions in metabolism, especially during times of fasting and stress (Tavares et al, 2023).GH increases food intake, fat mobilization, blood glucose levels, causes insulin resistance, produces changes in energy expenditure and modulates neuroendocrine responses during metabolic challenges. When all of these effects are considered in the context of metabolic stress situations, they contribute to restoring homeostasis by helping the body to use appropriate energy substrates, preventing hypoglycemia or increasing glucose availability, stimulating feeding to provide nutrients in response to activities that require energy or to accelerate the recovery of energy stores, and affect the activity of neuronal populations involved in controlling metabolism and the stress response (Tavares et al, 2023). Thus, the central and peripheral effects of GH coordinate multiple adaptations during situations of metabolic stress that, ultimately, help the organism to restore homeostasis, increasing the chances of survival (Mariana Rosolen Tavares, Renata Frazao and Jose Donato Jr. 2023).It is well established that the GH receptor is present in the dorsomedial nucleus of the hypothalamus (DMH) (Furigo et al., 2017). However, to date, it is not known what its functionality is in these neurons. Thus, our objective is to understand the importance of the GH receptor in DMH, inducing the inactivation of this receptor through injection of adeno-associated virus. Thus, we will be able to study aspects that are regulated by these neurons, and evaluate whether they are altered by the lack of GH signaling action.