Mehanovic, Samir Étudiant


Étudiant au doctorat

(1) Axe reproduction, santé de la mère et de l'enfant, Centre de recherche du CHU de Québec

(2) Département d'obstétrique, gynécologie et reproduction, Faculté de médecine

Expertises

leydig cells testosterone Steroidogenesis COUP-TF
: Doctorat
:

Global roles of the nuclear receptor COUP-TFII in steroidogenic Leydig cells  



Centre de recherche du CHU de Québec (CHUL)

2705 boul. Laurier
Québec (QC) Canada
G1V 4G2
(418) 525-4444 poste : 48821
Fax : 418-654-2783
samir.mehanovic.1@ulaval.ca

Laboratoire

Jacques J Tremblay

Niveau d'étude

Doctorat

Master of Science: Biochemistry, Iowa State University (Ames, Iowa, USA)

Bachelor of Science: Biology, Iowa State University (Ames, Iowa, USA)  


RÉSUMÉ DU PROJET DE RECHERCHE

Steroid hormones regulate essential physiological processes and inadequate levels are associated with numerous pathological conditions including hormone-dependent cancers. Life-threatening diseases as atherosclerosis, metabolic syndrome, and diabetes have been linked to testosterone deficiency, which is more prevalent in subfertile males. Steroidogenesis in Leydig cells is finely regulated to avoid hormone insufficiency or excess. Signals controlling Leydig cell differentiation and function have been characterized but the transcription factors (TFs) downstream of these pathways remain poorly understood. To date, a handful of TFs have been implicated in these processes. Our lab identified the nuclear receptor COUP-TFII in Leydig stem cells and in steroidogenically active adult, but not in fetal cells. We found that COUP-TFII regulates the expression of two key LC genes, Star and Insl3, and interact and cooperate with the nuclear receptor SF1. Microarray and qPCR from COUP-TFII-depleted LC revealed additional potential COUP-TFII targets including Amhr2, Inha and Hsd3b1. My hypothesis is that COUP-TFII is a critical regulator of Leydig cell differentiation and function. The general objective of my project is to determine how COUP-TFII acts in Leydig cells. I have 3 specific objectives: 1) to characterize of the role of COUP-TFII in the regulation of Amhr2, Inha and Hsd3b1 in Leydig cells using classical functional promoter assays in cell culture; 2) to define the genome-wide DNA binding activity of COUP-TFII in MLTC-1 Leydig cells by ChIP-Seq; 3) to elucidate the interactome of COUP-TFII in MLTC-1 Leydig cells using the TAP-Tag methodology. This project will provide invaluable insights regarding COUP-TFII in Leydig cells.