Low concentrations of the food contaminant Deoxynivalenol trigger apoptosis and impair GnRH-induced LH secretion in pituitary gonadotrope-like cells

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. Nearly all individuals are exposed to DON, due to it widespread presence in grains and grain-based products. Chronic DON poisoning is associated with growth retardation, immunotoxicity as well as impaired reproduction and fetal development. At the molecular level, DON alters intracellular signaling by activating mitogen-activated protein kinases (MAPKs) that modulate cell growth, differentiation, and apoptosis. Of note, these MAPKs are also critical mediators of gonadotrophin-releasing hormone (GnRH)-induced synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by pituitary gonadotrope cells. So far, no research has explored the potential endocrine-disrupting effects of DON on pituitary gonadotropins production. Herein, we show the first evidence that DON affects LH production by the immortalized gonadotrope-like cell line L{beta}T2 in a concentration-dependent manner. Taken together, our experiments demonstrated that low concentrations of DON affect GnRH-induced signaling through a mechanism that, at least in part, involves apoptosis and inhibition of GnRH-induced phosphorylation of ERK-MAPK. Consequently, DON also affects the GnRH-induced expression of Cga and Lhb, two critical genes for LH synthesis and secretion by gonadotrope cells in mammals. This research broadens our knowledge of the toxicity of DON and brings a new depth to the potential neuroendocrine implications for reproduction. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/607800v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@78d077org.highwire.dtl.DTLVardef@1be5bdaorg.highwire.dtl.DTLVardef@804d49org.highwire.dtl.DTLVardef@1520136_HPS_FORMAT_FIGEXP M_FIG C_FIG