Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor gamma/retinoid X receptor pathway.
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) gamma and retinoid X receptor. Because PPARgamma 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.
Kanayama
Tomohiko
T
Department of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kobayashi
Naoki
N
Mamiya
Satoru
S
Nakanishi
Tsuyoshi
T
Nishikawa
Jun-ichi
J
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D003001:Cloning, Molecular; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D009947:Organotin Compounds / Q000494:pharmacology*; D047495:PPAR gamma / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D047488:Retinoid X Receptors / Q000502:physiology*
D009947:Organotin Compounds; D047495:PPAR gamma; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors