PMID- 23583632
OWN - NLM
STAT- MEDLINE
DCOM- 20130712
LR  - 20131121
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 270
IP  - 1
DP  - 2013 Jul 1
TI  - Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR 
      and CYP19A1 expression in rat granulosa cells.
PG  - 1-8
LID - S0041-008X(13)00140-3 [pii]
LID - 10.1016/j.taap.2013.03.031 [doi]
AB  - Worldwide used herbicide atrazine is linked to reproductive dysfunction in 
      females. In this study, we investigated the effects and the mechanism of atrazine 
      action in the ovary using a primary culture of immature granulosa cells. In 
      granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic 
      adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) 
      cascades, with cAMP pathway being more important for luteinizing hormone receptor 
      (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48h after atrazine 
      exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol 
      synthesis were decreased, with LHR mRNA being more sensitive to atrazine than 
      CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and 
      atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) 
      ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone 
      receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To 
      dissect the signaling cascade involved in atrazine action in granulosa cells, we 
      used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents 
      atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production 
      in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability 
      of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa 
      cells. Cell-based ELISA assay revealed that atrazine does not change the 
      FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this 
      study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to 
      cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol 
      production in immature granulosa cells, thus compromising ovulation and female 
      fertility.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Fa, Svetlana
AU  - Fa S
AD  - Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of 
      Sciences, University of Novi Sad, 21000 Novi Sad, Serbia.
FAU - Pogrmic-Majkic, Kristina
AU  - Pogrmic-Majkic K
FAU - Samardzija, Dragana
AU  - Samardzija D
FAU - Glisic, Branka
AU  - Glisic B
FAU - Kaisarevic, Sonja
AU  - Kaisarevic S
FAU - Kovacevic, Radmila
AU  - Kovacevic R
FAU - Andric, Nebojsa
AU  - Andric N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130410
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Herbicides)
RN  - 0 (Nitriles)
RN  - 0 (Receptors, LH)
RN  - 0 (U 0126)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 1.14.14.1 (CYP19A1 protein, human)
RN  - QJA9M5H4IM (Atrazine)
SB  - IM
MH  - Animals
MH  - Aromatase/*biosynthesis
MH  - Atrazine/*pharmacology
MH  - Butadienes/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Follicle Stimulating Hormone/*pharmacology
MH  - Granulosa Cells/drug effects/*metabolism
MH  - Herbicides/pharmacology
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Nitriles/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, LH/*biosynthesis
EDAT- 2013/04/16 06:00
MHDA- 2013/07/16 06:00
CRDT- 2013/04/16 06:00
PHST- 2013/01/18 00:00 [received]
PHST- 2013/03/12 00:00 [revised]
PHST- 2013/03/22 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2013/07/16 06:00 [medline]
AID - S0041-008X(13)00140-3 [pii]
AID - 10.1016/j.taap.2013.03.031 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2013 Jul 1;270(1):1-8. doi: 10.1016/j.taap.2013.03.031. 
      Epub 2013 Apr 10.