Zearalenone activates GnRH neurons related to central precocious puberty by regulating microRNA-384/GPER signaling

Central precocious puberty (CPP) is an important issue, characterized as the same physical features as normally timed puberty occurs at an early age. Non-steroidal mycotoxins such as zearalenone (ZEA) are the important triggering factors for CPP development in girls; however, the detailed mechanism responsible for the effect of ZEA is still unclear.

In this study, the effect as well as the underlying mechanism of ZEA on cell proliferation and GnRH secretion in the mouse GnRH (gonadotropin-releasing hormone)-producing hypothalamic cell line GT1-7 were investigated.

The in vitro experiments revealed that ZEA treatment up-regulated cell proliferation as well as the expressions of GnRH and GPER (G protein-coupled estrogen receptor) in GT1-7 cells by down-regulating the expression of microRNA-384 (miR-384). However, such effects were attenuated by GPER inhibitor G15 pre-treatment. In addition, clinical samples analysis revealed that urinary ZEA in CPP patients significantly correlated to blood expressions of GPER and miR-384.

In conclusion, this study reveals a novel mechanism of ZEA on CPP using in vitro model and clinical samples, and which may provide a potential therapeutic target as well as the diagnostic biomarker for CPP.