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.
Keywords: Leydig cells; Nur77; Steroidogenic enzymes; Testosterone; Zearalenone.
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