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ORIGINAL ARTICLE

Organotin Compounds Promote Adipocyte Differentiation as Agonists of the Peroxisome Proliferator-Activated Receptor /Retinoid X Receptor Pathway

Departments of Environmental Biochemistry (T.K., N.K., S.M., J.N.) and Toxicology (T.N.), Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Abstract

Nuclear receptors play important roles in the maintenance of the endocrine system, regulation of organ differentiation, and fetal development. Endocrine disruptors exert their adverse effects by disrupting the endocrine system via various mechanisms. To assess the effects of endocrine disruptors on nuclear receptors, we developed a high-throughput method for identifying activators of nuclear receptors. Using this system, we found that triphenyltin and tributyltin were activators of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor. Because PPAR is a master regulator of adipocyte differentiation, we assessed the effect of organotin compounds on preadipocyte 3T3-L1 cells. We found that organotin compounds stimulated differentiation of 3T3-L1 cells as well as expression of adipocyte marker genes.

Received for publication October 18, 2004.

Accepted for publication December 20, 2004.

Address correspondence to: Dr. Jun-ichi Nishikawa, Department of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail: nisikawa{at}phs.osaka-u.ac.jp

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