Protein dissulfide isomerases (PDIs): relationship with sex steroid hormones and epididymal function

• Grant number: 17/05261-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2017
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Christina Werneck de Avellar
• Grantee: Samuel Guilerme Fernandes
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The protein disulfide isomerase (PDI) family is a member of the thioredoxin superfamily of redox proteins. It is composed of several multifunctional molecular chaperones that are involved with protein post-translational modifications. They differ greatly not only in amino acid sequence and molecular mass but also in domain composition and subcellular compartments location. Although mostly involved in disulfide bond formation, not all of them display conserved enzymatic activity. PDIs aresecreted under physiological conditions in the male gonad and have been shown tocontribute to the ability of the spermatozoa to fertilize an egg. Some have been alsoshown to bind steroid hormones in vitro, suggesting their potential to bind/sequester sex steroid hormones in male reproductive tract tissues. Therefore, our aim in the presentstudy is to identify the PDIs expressed in the epididymis, an important tissue for spermmaturation, during Wistar rat prenatal and postnatal development. We will specificallyevaluate: 1) the temporal mRNA expression profile of all 21 PDI family proteins in therat developing epididymis (prenatal, postnatal and adult); 2) the dependence of theexpression of epididymal PDIs on androgens and testicular factors; 3) the ability ofepididymal PDIs to bind steroid sex hormones. The results will increase our knowledgeon the molecular mechanisms by which protein quality control systems determine malereproductive function, essential for maximizing male fertility. The work will open up thePDI family for exploitation as potential drug targets and/or biomarkers in the malereproductive system. (AU)