Exposure to fenvalerate has been shown to be associated with decreased steroid hormone production by mouse Leydig tumor cells (MLTC-1) in our previous study and the interference with cAMP-PKA pathway cannot explain this inhibitory effect completely. In this study, the same cell line was used to investigate the potential involvement of insulin-like growth factor I (IGF-I) signaling pathway in the downregulation of steroidogenesis by fenvalerate. Results showed that fenvalerate treatment decreased IGF-I secretion significantly which was consistent with the reduced expression of IGF-I mRNA. Then inhibitors of the two downstream pathways of IGF-I were added to the medium. The addition of LY294002 (inhibitor of phosphatidylinositol (PI)-3-kinase) did not alter the declining trend of progesterone production with increasing dosages of fenvalerate treatment while the addition of UO126 (inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2)) markedly attenuated this trend, which strongly indicated the possible involvement of pathway ERK1/2. In addition, phosphorylation of ERK1/2 was also suppressed by fenvalerate. The results suggest that the mechanism by which fenvalerate decreased steroid hormone production might involve the impairment of IGF-I signal pathway by attenuating the IGF-I production and ERK1/2 phosphorylation.
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