Alterations of FSH-stimulated progesterone production and calcium homeostasis in primarily cultured human luteinizing-granulosa cells induced by fenvalerate

Toxicology. 2004 Oct 15;203(1-3):61-8. doi: 10.1016/j.tox.2004.05.014.

Abstract

Fenvalerate, a synthetic pyrethroid, is widely used in agriculture and other domestic applications in China. Recently, Fenvalerate has been suspected to be one of the endocrine-disrupting chemicals (EDC). In this study, we investigated the effects of fenvalerate on follicle-stimulating hormone (FSH)-stimulated progesterone (P4) production by human ovarian luteinizing-granulosa cells (hGLCs). After 24 h incubation, fenvalerate inhibited FSH-stimulated P4 production. At the same time, FSH-stimulated cAMP also decreased. Due to calcium and Ca2+ -calmodulin (CaM) system involving gonadotropin-stimulated steroidogenesis by granulosa cells, we then evaluated the effects of fenvalerate on trifluoperazine (TFP)- and verapamil-driven FSH-stimulated P4 production. The results showed that calcium or calmodulin might play a role in fenvalerate-induced alterations in FSH-stimulated P4 biosynthesis. Then, the effects of fenvalerate on calcium homeostasis in hGLCs were studied. The result showed that 5 microM fenvalerate induced a slow increase in [Ca2+]i in hGLCs by using a fluorescent Ca2+ indicator fluo-3/AM. The changes in total concentration of CaM in hGLCs induced by fenvalerate were evaluated by a method of immunofluorescence. There is a significant increase in all treated groups. In summary, fenvalerate could inhibit FSH-stimulated P4 production. Also, fenvalerate interferes with calcium homeostasis in hGLCs. The effects of fenvalerate on FSH-stimulated ovarian steroidogenesis may be mediated partly through calcium signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Calmodulin / metabolism
  • Cells, Cultured
  • Cyclic AMP / biosynthesis
  • Female
  • Fluorescent Antibody Technique
  • Follicle Stimulating Hormone / pharmacology*
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism*
  • Homeostasis / drug effects*
  • Humans
  • Insecticides / pharmacology*
  • Lutein / physiology*
  • Nitriles
  • Ovary / cytology
  • Ovary / drug effects
  • Ovary / metabolism
  • Progesterone / biosynthesis*
  • Pyrethrins / pharmacology*
  • Radioimmunoassay
  • Theca Cells / drug effects
  • Theca Cells / metabolism

Substances

  • Calmodulin
  • Insecticides
  • Nitriles
  • Pyrethrins
  • Progesterone
  • Follicle Stimulating Hormone
  • Cyclic AMP
  • Calcium
  • Lutein
  • fenvalerate