title: Zearalenone inhibits testosterone biosynthesis in mouse Leydig cells via the crosstalk of estrogen receptor signaling and orphan nuclear receptor Nur77 expression.
abstract: Zearalenone (ZEA) directly inhibits testosterone biosynthesis in Leydig cells, although the mechanisms involved remains unclear. Various experiments were performed to elucidate the molecular pathway of ZEA-mediated androgen inhibition. Leydig cells were isolated from 6 week-old male ICR mice and subjected to ZEA pre-treatment. The levels of testosterone and a series of influncing factors were measured. The results showed that ZEA caused a concentration- and time-dependent inhibition of testosterone stimulated both by hCG and cAMP (P<0.05). Exposure to ZEA did not affect the LHR binding activity nor the protein expression (P>0.05). However, ZEA exposure significantly elevated the cellular cAMP levels (P<0.05) in low concentrations (5 μg/ml) or for long time periods (24 h), significantly reduce the mitochondrial membrane potential (P<0.05). The expression of P450scc, 17β-HSD, and P450c17 at the mRNA level were significantly decreased (P<0.05). The steroidogenic acute regulatory (StAR) and 3β-HSD expression was significantly increased (P<0.05). Furthermore, the ERα protein expression was not affected by ZEA, but Nur77 expression was significantly inhibited (P<0.05). These observations imply that ZEA activity interferes with testosterone biosynthesis in mouse Leydig cells via the crosstalk of estrogen receptor signaling and Nur77 expression.
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Qing
authors: Q
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Yajun
authors: Y
authors: Wang
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Jianhong
authors: J
authors: Gu
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Yan
authors: Y
authors: Yuan
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Xuezhong
authors: X
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Wanglong
authors: W
authors: Zheng
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Qinyi
authors: Q
authors: Huang
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
authors: Zongping
authors: Z
authors: Liu
authors: College of Veterinary Medicine, Yangzhou University, 12 East, Wenhui Road, Yangzhou 225009, Jiangsu, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. Electronic address: jcbian@yzu.edu.cn.
authors: Jianchun
authors: J
authors: Bian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000502:physiology*; D011974:Receptors, LH; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000096:biosynthesis*; D015025:Zearalenone / Q000633:toxicity*
chemical_list: C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011960:Receptors, Estrogen; D011974:Receptors, LH; D013739:Testosterone; D015025:Zearalenone
keywords: Leydig cells; Nur77; Steroidogenic enzymes; Testosterone; Zearalenone