PPARalpha agonists clofibrate and gemfibrozil inhibit cell growth, down-regulate hCG and up-regulate progesterone secretions in immortalized human trophoblast cells.
ABSTRACT We studied effects of PPARalpha agonists clofibric acid and gemfibrozil on cell growth and functions of immortalized human extravillous trophoblast cells. Levels of DNA and protein gradually increased during incubation for 4 days. Gemfibrozil (>0.25mM) and clofibric acid (2.5mM) suppressed the rate of increase in DNA and protein. Specific activities of fatty acyl-CoA oxidase and catalase were increased to about 1.2-2.0 times the control value by 0.05mM gemfibrozil and 1.0 and 2.5mM clofibric acid after incubation for 3 days. Acid phosphatase activity showed a small increase in response to both agents, but esterase activity changed little. The secretion of progesterone from the cells into the medium was increased by 0.25mM gemfibrozil and 1.0 and 2.5mM clofibric acid after incubation for 3 days, but that of human chorionic gonadotropin (hCG) was decreased by 0.35mM gemfibrozil and 2.5mM clofibric acid. The specific activity of lactate dehydrogenase in the cells was hardly changed at all after incubation for 3 days. These results suggest that gemfibrozil and clofibric acid inhibit the proliferation of trophoblast cells. Cell metabolism is probably affected by both agents. The two agents may down-regulate hCG and up-regulate progesterone secretions.
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ABSTRACT: Emerging evidence indicates that fatty acid-activated nuclear transcription factors play very important and complex roles in placental biology. These fatty acid-activated receptors are involved at a number of different levels such as differentiation, proliferation, and hormone synthesis in the feto-placental unit. Since these receptors are also fatty acid sensors, they may be involved in placental fatty acid transport and metabolism. The present article is a review of the complex roles of peroxisome proliferator-activated receptors, sterol regulatory element-binding proteins and liver X receptors in placental biology.European Journal of Lipid Science and Technology 12/2005; 108(1):70 - 83. · 1.73 Impact Factor