Reference : Mechanisms of Interaction of Endocrine-Disrupting Chemicals with Glutamate-Evoked Sec...
Scientific journals : Article
Life sciences : Environmental sciences & ecology
Life sciences : Anatomy (cytology, histology, embryology...) & physiology
Mechanisms of Interaction of Endocrine-Disrupting Chemicals with Glutamate-Evoked Secretion of Gonadotropin-Releasing Hormone
Rasier, Gregory mailto [> > > >]
Parent, Anne-Simone mailto [Université de Liège - ULg > Département des sciences cliniques > Pédiatrie >]
Gerard, Arlette mailto [Centre Hospitalier Universitaire de Liège - CHU > > Pédiatrie >]
Denooz, Raphael mailto [Centre Hospitalier Universitaire de Liège - CHU > > Toxicologie clinique >]
Lebrethon, Marie-Christine mailto [Centre Hospitalier Universitaire de Liège - CHU > > Pédiatrie >]
Charlier, Corinne mailto [Université de Liège - ULg > Département de pharmacie > Chimie toxicologique]
Bourguignon, Jean-Pierre mailto [Université de Liège - ULg > Département des sciences cliniques > Pédiatrie - IFRES >]
Toxicological Sciences
Yes (verified by ORBi)
[en] In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT stimulated pulsatile gonadotropin-releasing hormone (GnRH) secretion and sexual maturation in the female rat. The aim of this study was to delineate the mechanisms of interaction of endocrine-disrupting chemicals including DDT with GnRH secretion evoked by glutamate in vitro. Using hypothalamic explants obtained from 15-day-old female rats, estradiol (E2) and DDT caused a concentration-related increase in glutamate-evoked GnRH release while p,p'-dichlorodiphenyldichloroethene and methoxychlor had no effect. The effective DDT concentrations in vitro were consistent with the serum concentrations measured in vivo 5 days after exposure of immature rats to 10 mg/kg/day of o,p'-DDT. Bisphenol A induced some stimulatory effect, whereas no change was observed with 4-nonylphenol. The o,p'-DDT effects in vitro were prevented partially by a selective antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptors. A complete prevention of o,p'-DDT effects was caused by an estrogen receptor (ER) antagonist as well as an aryl hydrocarbon receptor (AHR) antagonist and inhibitors of protein kinases A and C and mitogen-activated kinases. While an intermittent incubation with E2 caused no change in amplification of the glutamate-evoked GnRH release for 4 h, continuous incubation with E2 or o,p'-DDT caused an increase of this amplification after 3.5 h of incubation. In summary, DDT amplifies the glutamate-evoked GnRH secretion in vitro through rapid and slow effects involving ER, AHR, and AMPA receptor mediation.
Commission européenne : Direction générale de la Recherche ; Belgian study group for pediatric endocrinology ; Fonds Léon Fredericq

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