Effects of fenvalerate on steroidogenesis in cultured rat granulosa cells.
OBJECTIVE
This study was designed to examine the in vitro effects of fenvalerate on steroid production and steroidogenic enzymes mRNA expression level in rat granulosa cells.


METHODS
Using primary cultured rat granulosa cells (rGCs) as model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 micromol/L) was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)-hydroxycholesterol (25 micromol/L), Follicle stimulating hormone (FSH, 2 mg/L), or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17 beta-estradiol(E2) and progesterone (P4) in the medium from the same culture wells were measured by RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative RT-PCR.


RESULTS
Fenvalerate decreased both P4 and E2 production in a dose-dependent manner while it could significantly stimulate rGCs proliferation. This inhibition was stronger in the presence of FSH. Furthermore, it could not be reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that fenvalerate had no significant effect on 3 beta-HSD, but could increase the P450scc mRNA level. In addition, 17 beta-HSD mRNA level was dramatically reduced with the increase of fenvalerate dose after 24 h treatment.


CONCLUSIONS
Fenvalerate inhibits both P4 and E2 production in rGCs. These results support the view that fenvalerate is considered as a kind of endocrine-disrupting chemicals. The mechanism of its disruption may involve the effects on steroidogenesis signaling cascades and/or steroidogenic enzyme's activity.
Jiangsu Key Laboratory of Applied Toxicology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Jian-Feng
JF
Chen
Hai-Yan
HY
Chen
Ru
R
Liu
Jun
J
He
Lin
L
Song
Qian
Q
Bian
Li-Chun
LC
Xu
Jian-Wei
JW
Zhou
Hang
H
Xiao
Gui-Dong
GD
Dai
Xin-Ru
XR
Wang
D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000032:analysis / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006888:Hydroxycholesterols / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology*; D011374:Progesterone / Q000032:analysis / Q000378:metabolism; D011722:Pyrethrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D013256:Steroids / Q000378:metabolism*
D006888:Hydroxycholesterols; D009570:Nitriles; D011722:Pyrethrins; D012333:RNA, Messenger; D013256:Steroids; C003585:22-hydroxycholesterol; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases; C017690:fenvalerate