Endocrine disrupting effects of dichlorodiphenyltrichloroethane analogues on gonadotropin hormones in pituitary gonadotrope cells

Environ Toxicol Pharmacol. 2014 May;37(3):1194-201. doi: 10.1016/j.etap.2014.04.018. Epub 2014 Apr 20.

Abstract

It has been shown that exposure to dichlorodiphenyltrichloroethane (DDT) analogues leads to disharmony of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, the effects and mechanisms of DDT analogues on the expression of gonadotropin genes (FSHβ, LHβ and Cgα), which is the rate-limiting step of FSH and LH biosynthesis, remain unknown. In this study, we assessed the effects of p,p'-DDT, o,p'-DDT, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and methoxychlor (MXC) on gonadotropin genes expression and hormones synthesis in gonadotrope cells. p,p'-DDT and MXC at test concentrations ranging from 10(-9) to 10(-7)mol/L, stimulated gonadotropin genes expression and hormones synthesis in a dose-dependent manner. The activation of extracellular signal-regulated kinase (ERK) was required for the induction of gonadotropin genes expression and hormones synthesis by p,p'-DDT or MXC exposure. This study showed for the first time that p,p'-DDT and MXC regulated gonadotropin genes expression and hormones synthesis through ERK pathway in gonadotrope cells.

Keywords: Dichlorodiphenyltrichloroethane; Follicle-stimulating hormone; Luteinizing hormone; Methoxychlor; Pituitary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • DDT / toxicity*
  • Dichlorodiphenyl Dichloroethylene / toxicity*
  • Endocrine Disruptors / toxicity*
  • Gene Expression Regulation / drug effects
  • Gonadotropins / genetics*
  • Gonadotropins / metabolism
  • Methoxychlor / toxicity*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • Pituitary Gland / cytology
  • RNA, Messenger / metabolism

Substances

  • Endocrine Disruptors
  • Gonadotropins
  • RNA, Messenger
  • Dichlorodiphenyl Dichloroethylene
  • DDT
  • o,p'-DDT
  • Mitogen-Activated Protein Kinases
  • Methoxychlor