[POSTER] The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hypothalamus-pituitary-gonadal (HPG) axis in female rat primary cultures

Research Area: Uncategorized Year: 2013
Type of Publication: In Proceedings
  • Solak, K.A.
  • Wijnolts, F.
  • Blaauboer, B.
  • van den Berg, M
  • van Duursen, M.
Book title: The Toxicologist
Organization: Society of Toxicology
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) belongs to a group of structurally persistent, highly lipophilic compounds, that exerts a variety of adverse effects on the development and physiology of the reproductive system. TCDD and other dioxin-like PCBs act as endocrine disruptive compounds (EDCs) on the hypothalamus-pituitary-gonad (HPG) reproductive axis, mainly through the activation of aryl hydrocarbon receptor (AHR) signaling. Females are believed to display higher sensitivity to TCDD mainly due to the sex differences in adipose tissue percentage and thus higher accumulation of TCDD in female tissues, including ovaries. The present study was designed to explore the mechanisms of endocrine disrupting properties of TCDD on female adult rat hypothalamus–pituitary-gonadal axis (HPG axis) in vitro by employing primary hypothalamus, pituitary and ovaria cultures. In all HPG axis compartments, TCDD elevated its sensitive markers CYP1a1 and AhRR after 24hours. No changes in gonadotropin-releasing hormone (GnRH) and gonadotropins mRNA and protein levels were observed after 10nM TCDD treatment. TCDD exerted its anti-estrogenic effects by alteration of the crucial enzymes in ovarian steroidogenesis. Significant down-regulation of CYP17 and CYP19 mRNA levels were observed with a slight decrease of estradiol levels after 24 hours. Furthermore, the FSH receptor was significantly down-regulated by TCDD, indicating that TCDD may disturb the HPG axis via this receptor by modulation of ovarian response to gonadotropins. This process may which further lead to ovarian desensitization. To investigate the AhR involvement in these enzyme and receptor mRNA observed changes, siRNA against AhR was applied. The results suggest a key role of the AhR in CYP19 gene regulation in the regulation of female reproductive tract.
Full text: poster Solak.pdf
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