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

• Grant number: 17/25281-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2018
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Jose Donato Junior
• Grantee: Paula Gabriele Fernandes Quaresma Bergonsi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease, AP.TEM

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.

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

QUARESMA, PAULA G. F.; WASINSKI, FREDERICK; MANSANO, NAIRA S.; FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; GUSMAO, DANIELA O.; FRAZAO, RENATA; DONATO JR, JOSE. Leptin Receptor Expression in GABAergic Cells is Not Sufficient to Normalize Metabolism and Reproduction in Mice. Endocrinology, v. 162, n. 11, NOV 2021. (21/03316-5, 16/09679-4, 19/21707-1, 17/25281-3, 20/01318-8, 17/22189-9, 16/20897-3)

QUARESMA, PAULA G. F.; TEIXEIRA, PRYSCILA D. S.; WASINSKI, FREDERICK; CAMPOS, ANA M. P.; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO, JR., JOSE. Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone. Life Sciences, v. 259, OCT 15 2020. (17/02983-2, 17/25281-3, 16/20897-3)

FURIGO, ISADORA C.; SUZUKI, MIRIAM F.; OLIVEIRA, JOAO E.; RAMOS-LOBO, ANGELA M.; TEIXEIRA, PRYSCILA D. S.; PEDROSO, JOAO A.; DE ALENCAR, AMANDA; ZAMPIERI, THAIS T.; BUONFIGLIO, DANIELLA C.; QUARESMA, PAULA G. F.; et al. Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice. Endocrinology, v. 160, n. 1, p. 193-204, JAN 2019. (13/25032-2, 14/11752-6, 15/10992-6, 12/15517-6, 13/21722-4, 17/25281-3, 12/24345-4)

QUARESMA, PAULA G. F.; TEIXEIRA, PRYSCILA D. S.; FURIGO, ISADORA C.; WASINSKI, FREDERICK; COUTO, GISELE C.; FRAZAO, RENATA; LIST, EDWARD O.; KOPCHICK, JOHN J.; DONATO JR, JOSE. Growth hormone/STAT5 signaling in proopiomelanocortin neurons regulates glucoprivic hyperphagia. Molecular and Cellular Endocrinology, v. 498, DEC 1 2019. (16/20897-3, 16/09679-4, 17/04006-4, 17/02983-2, 17/21840-8, 17/25281-3)

CHAVES, FERNANDA M.; WASINSKI, FREDERICK; TAVARES, MARIANA R.; MANSANO, NAIRA S.; FRAZAO, RENATA; GUSMAO, DANIELA O.; QUARESMA, PAULA G. F.; PEDROSO, JOAO A. B.; ELIAS, CAROL F.; LIST, EDWARD O.; et al. Effects of the Isolated and Combined Ablation of Growth Hormone and IGF-1 Receptors in Somatostatin Neurons. Endocrinology, v. 163, n. 5, p. 13-pg., 2022-05-01. (16/20897-3, 17/25281-3, 20/01318-8, 20/10102-9, 19/21707-1, 17/21854-9, 17/22189-9, 21/03316-5)

FURIGO, ISADORA C.; TEIXEIRA, PRYSCILA D. S.; QUARESMA, PAULA G. F.; MANSANO, NAIRA S.; FRAZAO, RENATA; DONATO JR, JOSE. STAT5 ablation in AgRP neurons increases female adiposity and blunts food restriction adaptations. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 64, n. 1, p. 13-27, JAN 2020. (17/22189-9, 17/02983-2, 17/25281-3, 16/09679-4, 17/21840-8)

WASINSKI, FREDERICK; BARRILE, FRANCO; PEDROSO, JOAO A. B.; QUARESMA, PAULA G. F.; DOS SANTOS, WILLIAN O.; LIST, EDWARD O.; KOPCHICK, JOHN J.; PERELLO, MARIO; DONATO, JR., JOSE. Ghrelin-induced Food Intake, but not GH Secretion, Requires the Expression of the GH Receptor in the Brain of Male Mice. Endocrinology, v. 162, n. 7, JUL 2021. (20/01318-8, 16/20897-3, 17/25281-3)

QUARESMA, PAULA G. F.; DOS SANTOS, WILLIAN O.; WASINSKI, FREDERICK; METZGER, MARTIN; DONATO JR, JOSE. Neurochemical phenotype of growth hormone-responsive cells in the mouse paraventricular nucleus of the hypothalamus. JOURNAL OF COMPARATIVE NEUROLOGY, v. 529, n. 6, SEP 2020. (17/02983-2, 16/20897-3, 17/25281-3, 17/16473-6)