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The role of POMC-derived peptides in differentiation and function of adrenal cortex

Grant number: 12/23535-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2013
Effective date (End): February 28, 2017
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Claudimara Ferini Pacicco Lotfi
Grantee:Pedro Omori Ribeiro de Mendonça
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):14/04758-8 - Characterization of N-terminal POMC peptide receptor, BE.EP.PD

Abstract

Studies using knock-out mice models for the gene pro-opiomelanocortin (Pomc-/-) have demonstrated that animals which survive to adult were obese, with defects in pigmentation and had severe adrenal insufficiency. When newborns, adrenal gland was present macroscopically, however, five weeks after the birth, there is a severe atrophy of the entire organ, reflecting the dependency of POMC derived peptides for maturation and maintenance of the adrenal. The adrenocorticotropic hormone (ACTH) is considered the main peptide derived from POMC acting in the adrenal gland development, maintenance and corticosteroidogenesis. Although there is evidence that other peptides derived from POMC such as peptides from the N-terminal (N-POMC), may act to maintain the adrenal gland, it remains unclear the importance of the role of these peptides in the terminal differentiation, maturation, and function of the adrenal cortex. Animals that have a conditional knock-out Pomc gene controlled by a Cre-Lox tamoxifen-inducible system, will allow us to study the effects of knock-down Pomc gene in specific periods of development (neonate or young adult) and assess the role of different types of N-POMC peptides, synthetic or extracts, in the architecture and function of the adrenal gland, food intake and body weight. The architecture of the gland will be analyzed by immunofluorescence using antibodies to detect proliferating and apoptotic cells, steroidogenic enzymes, specific marker for fetal zone (zone X) besides the detection of extracellular matrix proteins and vessels. The functional capacity of the adrenal gland will be analyzed by quantification of plasma corticosterone and aldosterone in the blood. We expect the results obtained help to elucidate the role of N-POMC peptides in the development, maturation and function of the adrenal gland.

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Scientific publications
(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)
PEDROSO, JOAO A. B.; DE MENDONCA, PEDRO O. R.; FORTES, MARCO A. S.; TOMAZ, IGOR; PECORALI, VITOR L.; AURICINO, THAIS B.; COSTA, ISMAEL C.; LIMA, LEANDRO B.; FURIGO, ISADORA C.; BUENO, DEBORA N.; et al. SOCS3 expression in SF1 cells regulates adrenal differentiation and exercise performance. Journal of Endocrinology, v. 235, n. 3, p. 207-222, . (10/18086-0, 12/23535-4, 13/21722-4, 14/11752-6, 14/50140-6, 15/10992-6)
IMENEZ SILVA, PEDRO HENRIQUE; MELO, DIOGO; RIBEIRO DE MENDONCA, PEDRO OMORI. Insights from Systems Biology in Physiological Studies: Learning from Context. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 42, n. 3, p. 939-951, . (12/23535-4, 14/26262-4)

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