Differential effects of the persistent DDT metabolite methylsulfonyl-DDE in nonstimulated and LH-stimulated neonatal porcine Leydig cells

Toxicol Appl Pharmacol. 2013 Mar 15;267(3):247-55. doi: 10.1016/j.taap.2012.12.022. Epub 2013 Jan 17.

Abstract

3-Methylsulfonyl-DDE (MeSO₂-DDE) is a potent adrenal toxicant formed from the persistent insecticide DDT. MeSO₂-DDE is widely present in human plasma, milk and fat, and in tissues of marine mammals. In the present study, we investigated endocrine-disrupting properties of MeSO₂-DDE in primary neonatal porcine Leydig cells. Unstimulated and LH-stimulated cells were exposed to MeSO₂-DDE at concentrations ranging from 0.6 to 20 μM for 48 h. Cell viability, hormone secretion and expression of steroidogenesis related genes were recorded. Secretion of testosterone and estradiol was increased in a concentration-dependent fashion in unstimulated Leydig cells, while in LH-stimulated cells, secretion of testosterone, estradiol and progesterone was decreased. The expression of important steroidogenic genes was down-regulated both in unstimulated and LH-stimulated cells. Notably, no significant impairment of cell viability occurred at any exposure except the highest concentration (20 μM) in LH-stimulated cells. This indicated that the effects on hormone secretion and gene expression were not caused by cytotoxicity. We conclude that the adrenal toxicant MeSO₂-DDE disrupts hormone secretion in a complex fashion in neonatal porcine Leydig cells. The different endocrine responses in unstimulated and LH-stimulated cells imply that the endocrine disruptive activity of MeSO₂-DDE is determined by the physiological status of the Leydig cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • DDT / metabolism
  • DDT / toxicity*
  • Dichlorodiphenyl Dichloroethylene / metabolism
  • Dichlorodiphenyl Dichloroethylene / toxicity*
  • Endocrine Disruptors / toxicity*
  • Leydig Cells / drug effects*
  • Leydig Cells / metabolism
  • Luteinizing Hormone / toxicity*
  • Male
  • Swine

Substances

  • Endocrine Disruptors
  • Dichlorodiphenyl Dichloroethylene
  • Luteinizing Hormone
  • DDT