Involvement of IGF-I signaling pathway in the regulation of steroidogenesis in mouse Leydig cells treated with fenvalerate.
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.
School of Public Health, NanTong University, 9 Seyuan Road, Nantong 226019, China.
Jian-Hua
JH
Qu
Juan
J
Fei
Xia
X
Hong
Jian-Feng
JF
Chen
Ai-Hua
AH
Gu
Hong
H
Sun
Xiao-Lin
XL
Xu
Ling
L
Song
Shou-Lin
SL
Wang
Xin-Ru
XR
Wang
D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011374:Progesterone / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011722:Pyrethrins / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013737:Testis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011722:Pyrethrins; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011374:Progesterone; D012313:RNA; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; C017690:fenvalerate