Peroxisome proliferators and retinoids affect JEG-3 choriocarcinoma cell function

Area of Science:

• Cell Biology
• Endocrinology
• Nutritional Science

Background:

• Nutritional signals are hypothesized to regulate trophoblast cell function.
• Peroxisome proliferator-activated receptors (PPARs) mediate lipidic nutrient effects on gene expression.
• PPARs interact with retinoid-X receptors, influencing their activity.

Purpose of the Study:

• To investigate the hypothesis that nutritional signals regulate trophoblast cell function using JEG-3 cells.
• To examine the effects of PPAR stimulators, alone and with retinoids, on JEG-3 cell function.
• To determine if PPAR stimulation induces peroxisome proliferation in JEG-3 cells.

Main Methods:

• JEG-3 choriocarcinoma cells were treated with PPAR-stimulating drugs (clofibric acid, WY 14,643) and retinoids.
• Cell growth, chorionic gonadotropin (CG) secretion, and related messenger RNA (mRNA) levels were assessed.
• Peroxisome proliferation was evaluated using electron microscopy and catalase immunostaining.
• Expression of PPARs (NUC1) and related genes was analyzed via mRNA levels.

Main Results:

• PPAR stimulation (clofibric acid, WY 14,643) suppressed JEG-3 cell growth and CG secretion.
• PPAR stimulation increased tumor suppressor p53 protein and mRNA but did not induce peroxisome proliferation.
• Retinoids increased CG secretion and mRNA, but PPAR stimulators blunted these effects.
• JEG-3 cells express NUC1 mRNA, which is upregulated by 8-bromo-cAMP.

Conclusions:

• JEG-3 cells express functional PPARs and respond to PPAR stimulators.
• PPAR stimulation in JEG-3 cells does not lead to peroxisome proliferation.
• PPARs and retinoids exert differential regulatory effects on JEG-3 cell endocrine functions, indicating nutrient responsiveness.