作者: Jing Liu , Ye Yang , Yan Yang , Ying Zhang , Weiping Liu
DOI: 10.1016/J.TOX.2011.01.007
关键词:
摘要: Synthetic pyrethroids (SPs) are one of the most frequently and widely used classes pesticides. Although exposure to SPs is associated with reproductive toxicity in mammals, limited information available regarding effects on female ovulatory function. Bifenthrin (BF), a broad-spectrum type I SP, has been for pest control two decades. Previous studies showed that BF had estrogen-like activity as an endocrine-disrupting chemical. In this work, we vitro inhibitory luteinizing hormone (LH)-inducible gene expression rat ovarian granulosa cells, including genes P450scc, StAR, PR, AREG, EREG, TGF-β1, C/EBP β, RUNX1, p21, cyclin E1, CYP19a1, SULT1E1 PTGS2. Our vivo demonstrated short-term administration gonadotropin-primed rats disrupted LH-responsible genes, suggesting similar disrupting LH signaling. Because prostaglandins their key synthetic enzyme PTGS2 play pivotal roles process, further investigated molecular mechanism disruption by BF. Importantly, found blocked LH-inducible prostaglandin E2 (PGE2) accumulation cultured medium cells. Forskolin stimulated was decreased treatment BF, indicating may inhibit LH-induced through protein kinase A (PKA)-mediated signaling pathway. addition, reduction transcriptional forskolin-stimulated promoter indicates blocks at level. Taken together, our present study firstly shows systemic network patterns well synthesis, suggest increase risk dysfunction females.