Effects of WY-14643 on peroxisomal enzyme activity and hormone secretion in immortalized human trophoblast cells.

In our previous report, clofibric acid increased both the enzyme activities of peroxisomes (catalase and fatty acyl-CoA oxidase) and the secretion of progesterone in immortalized human extravillous trophoblast cells (TCL-1) (F. Hashimoto et al., Biochem. Pharm., 68, 313 (2004)). WY-14643 is reported to be stronger inducer of peroxisomes in rodents than clofibric acid. Therefore, the effects of WY-14643 on the activities of peroxisomal enzymes and hormone secretion in TCL-1 were studied. After incubation for 3 d with WY-14643, WY-14643 (>/=0.15 mM) suppressed the rate of increase in DNA and protein. The specific activities of catalase were increased by 0.1 mM WY-14643. The specific activities of fatty acyl-CoA oxidase were hardly changed by WY-14643. The concentration of progesterone in the medium was increased by 0.1 mM WY-14643, but human chorionic gonadotropin was decreased by 0.2 mM WY-14643. After a discontinuous Nycodenz-density gradient centrifugation of the light mitochondrial fraction of the cells, catalase activity was distributed in lower density fractions than cytochrome-c oxidase (a mitochondria marker enzyme) activity, but the distribution was not changed by WY-14643. These results suggest that WY-14643 inhibits the proliferation of trophoblast cells. The density of peroxisomes in human trophoblast cells is lower than that of mitochondria, and it is not affected by WY-14643. WY-14643 may increase the progesterone secretion. Effects of WY-14643 on metabolism of human trophoblast cells are different from those of clofibric acid.