Document Detail


Carbaryl inhibits basal and FSH-induced progesterone biosynthesis of primary human granulosa-lutein cells.
MedLine Citation:
PMID:  16413094     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Carbaryl is known to impede female reproductive function, however, the mechanisms through which the adverse effects are mediated are not clearly elucidated. In order to get insight into the mechanisms, this study was conducted to raise fresh concerns about the potential effects of carbaryl on steroidogenesis by primary human granulosa-lutein cells (hGLCs) and explore the possible nature of this action. hGLCs were co-incubated with various concentrations of carbaryl at 0, 1, 5, 25, 125 micromol/L for 24 h to examine effects of this carbamate pesticide on progesterone accumulation. We observed that the carbaryl inhibited basal and FSH-induced progesterone production in a dose-dependent manner. We also investigated the effects of carbaryl on 22(R)-hydroxycholesterol (22R-HC)-stimulated progesterone yield, basal and FSH-stimulated StAR gene expression and cyclic adenosine monophosphate (cAMP) production, as well as forskolin (non-specific activator of adenylyl cyclase)-induced progesterone and cAMP production of hGLCs. We found that the decreased progesterone biosynthesis was accompanied with a reduced cAMP abundance on both basal and FSH-induced condition. Furthermore, our results demonstrated that the 22R-HC could remove the carbaryl-induced restraint of progesterone biosynthesis, suggesting that carbaryl caused a disruption of cholesterol transport across mitochondrial membranes, which was further confirmed by the observation that carbaryl inhibited the gene expression of steroidogenic acute regulatory protein (StAR). In addition, the inhibitory effects of carbaryl on progesterone and cAMP production were completely reversed by addition of forskolin to the cell culture, which indicated a repaired site on the upstream components of adenylate cyclase or adenylate cyclase per se by carbaryl in the cAMP-mediated signal pathway. All the effects mentioned above were not due to a detrimental action of carbaryl on cell viability by MTS assay. In conclusion, carbaryl may inhibit steroidogenesis, at least in part, by obstructing the delivery of cholesterol over mitochondrial membranes and attenuating cAMP generation.
Authors:
Senping Cheng; Jianfeng Chen; Yang Qiu; Xia Hong; Yankai Xia; Ting Feng; Jiayin Liu; Lin Song; Zhengdong Zhang; Xinru Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-01-18
Journal Detail:
Title:  Toxicology     Volume:  220     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-07     Completed Date:  2006-03-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  37-45     Citation Subset:  IM    
Affiliation:
Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, PR China.
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MeSH Terms
Descriptor/Qualifier:
Carbaryl / toxicity*
Cells, Cultured
Cyclic AMP / metabolism
Dose-Response Relationship, Drug
Drug Combinations
Female
Follicle Stimulating Hormone / pharmacology*
Forskolin / pharmacology
Gene Expression / drug effects
Granulosa Cells / drug effects*,  metabolism
Humans
Hydroxycholesterols / pharmacology
Pesticides / toxicity*
Phosphoproteins / genetics,  metabolism
Progesterone / biosynthesis*
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Hydroxycholesterols; 0/Pesticides; 0/Phosphoproteins; 0/RNA, Messenger; 0/steroidogenic acute regulatory protein; 17711-16-9/22-hydroxycholesterol; 57-83-0/Progesterone; 60-92-4/Cyclic AMP; 63-25-2/Carbaryl; 66428-89-5/Forskolin; 9002-68-0/Follicle Stimulating Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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