DOI: 10.1101/477901Nov 23, 2018Paper

Towards understanding biology of leydiogioma. G protein-coupled receptor and peroxisome proliferator-activated receptor crosstalk regulates lipid metabolism and steroidogenesis in Leydig cell tumors

BioRxiv : the Preprint Server for Biology
Malgorzata Kotula-BalakJan K Wolski

Abstract

Leydig cell tumors (LCT) are the most common type of testicular sex cord-stromal tumor. In this report, we implicate the G-coupled estrogen receptor (GPER) and peroxisome proliferator receptor (PPAR) in regulation of lipid homeostasis and the expression of steroidogenesis-controlling molecules in clinical specimens of LCTs and cell line (mouse tumor Leydig cells; MA-10). We also show the general structure and morphology of human LCTs with the use of scanning electron microscopy and light microscopy, respectively. In LCTs, protein immunoblotting and immunohistochemical analysis revealed increased expression of GPER and decreased expression of PPARα, β and γ. Concomitantly, changes in expression pattern of the lutropin receptor (LHR), protein kinase A (PKA), perilipin (PLIN), hormone sensitive lipase (HSL), steroidogenic acute regulatory protein (StAR), translocator protein (TSPO), HMG-CoA synthase (HMGCA), and HMG-CoA reductase (HMGCR) were observed. Using MA-10 cells treated with GPER and PPAR antagonists (alone and in combination), we demonstrated there is a GPER-PPAR mediated control of cholesterol concentration. In addition, GPER-PPARα regulated estradiol secretion, while GPER-PPARγ affected cGMP concentration. It is assumed...Continue Reading

Related Concepts

Cholesterol
Sterol esterase
Guanosine
Cyclic GMP
Hydroxymethylglutaryl-CoA reductase
Hydroxymethylglutaryl-CoA Synthase
Immunoblotting
Immunohistochemistry
Leydig Cell Tumor
Structure of Interstitial Cell of Leydig

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