Alterations of FSH-stimulated progesterone production and calcium homeostasis in primarily cultured human luteinizing-granulosa cells induced by fenvalerate.
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.
He
Jun
J
Jiangsu Key Laboratory of Applied Toxicology, Nanjing Medical University, 140 Hanzhong Road, 210029, China.
Chen
Jianfeng
J
Liu
Ru
R
Wang
Shoulin
S
Song
Lin
L
Chang
Hebron C
HC
Wang
Xinru
X
D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D014975:Lutein / Q000502:physiology*; D009570:Nitriles; D010053:Ovary / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*; D011722:Pyrethrins / Q000494:pharmacology*; D011863:Radioimmunoassay; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism
D002147:Calmodulin; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D002118:Calcium; D014975:Lutein; C017690:fenvalerate