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Analysis of action of the N-terminal POMC in the adrenal cortex atrophy of mice POMC-/- induced by Tamoxifen

Grant number: 15/06545-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2015
Effective date (End): December 31, 2015
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Claudimara Ferini Pacicco Lotfi
Grantee:Thais Barabba Auricino
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The proopiomelanocortin (POMC) is a prohormone of 241 amino acids mainly produced by the pituitary. After processing it results at various peptides such as adrenocorticotrophic hormone (ACTH). Studies with animals POMC - / -showed that animals which survive to adulthood are obese, with pigmentation defects and severe adrenal insufficiency, reflecting the dependency of the POMC derived peptides to adrenal maturation and maintenance. ACTH is the main factor derived from POMC acting in the development, maintenance or corticosteroidogênese of adrenal gland. Although there is evidence that the peptides of the N-terminal portion of POMC (N-POMC) can act in the maintenance of the adrenal gland, has not been established the importance of these peptides in the terminal differentiation, maturation, and function of the adrenal cortex. Through the use of animals with a system "knockout" Cre-Lox conditional inducible by tamoxifen for the silencing of POMC gene, which were obtained in our laboratory, we will silence the POMC gene in mice in a specific period of development. Through the administration of ACTH or N-terminal peptides of POMC in induced animals POMC- / - we will analyze the capacity to prevent or reverse, at least partially, the atrophy and loss of function caused by the absence of peptides derived from the POMC. Morphological analysis of cells and adrenal zones will be conducted by using light microscope and histological sections stained with hematoxylin and eosin of Putt (HE). In addition, a morphometric analysis for linear quantification of changes in the size of the adrenal cortex zones will be performed. To make sure that the animals used in this study are HPA axis blocked the concentration of circulating ACTH will be analyzed.

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