Inhibitory Effects of a Novel PPAR- γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.

Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells.
PPAR Res. 2018;2018:5346272
Authors: Parvin R, Noro E, Saito-Hakoda A, Shimada H, Suzuki S, Shimizu K, Miyachi H, Yokoyama A, Sugawara A
Abstract
Although therapeutic effects of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists rosiglitazone and pioglitazone against Cushing's disease have been reported, their effects are still controversial and inconsistent. We therefore examined the effects of a novel PPAR-γ agonist, MEKT1, on Pomc expression/ACTH secretion using murine corticotroph-derived AtT20 cells and compared its effects with those of rosiglitazone and pioglitazone. AtT20 cells were treated with either 1 nM~10 μM MEKT1, rosiglitazone, or pioglitazone for 24 hours. Thereafter, their effects on proopiomelanocortin gene (Pomc) mRNA expression were studied by qPCR and the Pomc promoter (-703/+58) activity was demonstrated by luciferase assay. Pomc mRNA expression and promoter activity were significantly inhibited by MEKT1 at 10 μM compared to rosiglitazone and pioglitazone. SiRNA-mediated PPAR-γ knockdown significantly abrogated MEKT1-mediated Pomc mRNA suppression. ACTH secretion from AtT20 cells was also significantly inhibited by MEKT1. Deletion/point mutant analyses of Pomc promoter indicated that the MEKT1-mediated suppression was mediated via NurRE, TpitRE, and NBRE at -404/-383, -316/-309, an...

Source: PPAR Research - June 1, 2018 Category: Genetics & Stem Cells Tags: PPAR Res Source Type: research