Sonic Hedgehog (SHH) signalling in adrenal steroidogenesis

• Grant number: 14/15517-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2014
• End date: October 31, 2016
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Sonir Roberto Rauber Antonini
• Grantee: Maíra Fassoni Ribeiro
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Background: recent data pointed to the role of the sonic Hedgehog (SHH) signaling pathway in adrenal cortex and capsule development and maintenance. Disruption of this pathway may be involved in adrenal tumorigenesis. Preliminary data generated in our Laboratory point to the potential involvement of SHH signaling in adrenal cortex steroidogenesis. Aim: to examine the role of the SHH pathway in adrenal cortex steroidogenesis. Methods: in vitro, NCI-H295 adrenal cells will be treated with Cyclopamine (an SHH inhibitor), metyrapone (an inhibitor of adrenal steroidogenesis) and controls (Tomatidine and DMSO) under different concentrations during 24h to 96h. We will evaluated the effect of these substances on cell viability, on the gene expression of SHH components (SHH, GLI1, GLI2, GLI3, SMO and PTCH) as well as genes involved in steroidogenesis (CYP11A1, CYP11A2, STAR, CYP17, HSD3B1 e PORB5) and on hormone secretion (SDHEA, testosterone, androstenedione and aldosterone). If our hypothesis is confirmed, this study will provide the first evidences of the SHH signaling acting on adrenal steroidogenesis.