PMID: 8946564Nov 1, 1996Paper

Mechanism of toxic action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in cultured human luteinized granulosa cells

Reproductive Toxicology
E EnanB L Lasley

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) caused a significant decrease in estradiol (E2) production when it was administered to human luteinized granulosa cells (hLGCs) in culture. We investigated the involvement of the epidermal growth factor receptor (EGFR) and protein tyrosine kinase (PTK) in this TCDD-induced toxicity. Upregulation in 125I-EGF binding to EGFR was measured after 24 h of TCDD treatment, while downregulation in EGFR binding was measured after 72 h of TCDD treatment. Upregulation of EGFR binding was associated with a significant decrease in postnuclear (7000 x g supernatant) PTK activity, but this activity was stimulated after 72 h of TCDD treatment. TCDD altered the level of tyrosine phosphorylation in proteins with molecular weights 35, 40, 43, 45, 60, and > 205 kDa. TCDD caused a significant increase in postnuclear cAMP-dependent protein kinase (PKA) after 24 h of treatment. The actions of TCDD on protein kinases were partially blocked by the protein synthesis inhibitor, cycloheximide. On the other hand, TCDD increased nuclear PTK and decreased nuclear PKA activity. E2 inhibited the postnuclear and nuclear activity of both PTK and PKA in control samples, but did not affect TCDD actions on either postnuclea...Continue Reading

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Citations

Jun 15, 2005·Archives of Biochemistry and Biophysics·J D VidalA J Conley
Sep 9, 2010·Molecular Human Reproduction·Katja HorlingBernd Fischer
Apr 22, 2006·The Journal of Reproduction and Development·H M HoReinhold J Hutz
Apr 14, 2007·Environmental Health Perspectives·Marcella WarnerPaolo Mocarelli
Aug 14, 1998·Environmental Health Perspectives·B L Lasley, J W Overstreet
Nov 18, 2008·Biochemical Pharmacology·Barbara Oesch-Bartlomowicz, Franz Oesch
Jul 25, 2006·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·J A OdumaD W Makawiti
Jun 30, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·J Thomas Sanderson

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