Evaluation of the effects of GLP-1 receptor ablation in GH-releasing hormone-secreting neurons

• Grant number: 24/05182-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2024
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Jose Donato Junior
• Grantee: Luís Fernando de Almeida
• 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

The hypothalamus plays a role in regulating the organism's homeostasis. Part of this control occurs through the integration between the nervous and endocrine systems by hypothalamic nuclei, which regulate hormone secretion by the adenohypophysis based on neural and hormonal stimuli. Growth hormone (GH) is produced by the adenohypophysis and exerts its effects on various tissues after being released into circulation. Its secretion is stimulated by growth hormone-releasing hormone (GHRH) and inhibited by somatostatin, among other factors. GLP-1 is a hormone produced by enteroendocrine L cells and promotes the reduction of glucagon secretion and increase of insulin secretion, as well as delaying gastric emptying, distending the smooth muscle of the stomach, reducing stomach acid secretion, and promoting greater satiety. GLP-1 receptors (GLP1-R) are expressed in various tissues. Agonist medications of GLP-1R, such as Ozempic, have been successfully used in the treatment of obesity and diabetes. Recently, a study identified that 47.9% of hypothalamic neurons expressing GHRH also express GLP-1R, suggesting a possible role of GLP-1 in controlling the GH axis. This study aims to investigate this role through the generation of mice subjected to ablation of GLP-1R in this neuronal population. The results obtained may expand the current understanding of GH physiology and provide elements to guide future clinical applications, as these medications have been the subject of clinical studies in children and adolescents, a period in which GH is crucial for somatic growth.