{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T17:26:50Z","timestamp":1778434010287,"version":"3.51.4"},"posted":{"date-parts":[[2024,8,16]]},"group-title":"Pharmacology and Toxicology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>Fusarium<\/jats:italic>\n                  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\u03b2T2 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\n                  <jats:italic>Cga<\/jats:italic>\n                  and\n                  <jats:italic>Lhb<\/jats:italic>\n                  , 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.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"607800v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2024.08.13.607800","type":"posted-content","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T21:50:15Z","timestamp":1723845015000},"source":"Crossref","is-referenced-by-count":1,"title":["Low concentrations of the food contaminant Deoxynivalenol trigger apoptosis and impair GnRH-induced LH secretion in pituitary gonadotrope-like 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