2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) decreases progesterone synthesis through cAMP-PKA pathway and P450scc downregulation in mouse Leydig tumor cells. Han, X., Tang, R., Chen, X., Xu, B., Qin, Y., Wu, W., Hu, Y., Xu, B., Song, L., Xia, Y., & Wang, X. Toxicology, 302(1):44--50, December, 2012.
2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) decreases progesterone synthesis through cAMP-PKA pathway and P450scc downregulation in mouse Leydig tumor cells. [link]Paper  doi  abstract   bibtex   
Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in textiles, plastics and electronics and represent a group of persistent environmental contaminants. They have been found to accumulate in human and marine mammals. Previous studies have shown that PBDEs have endocrine-disrupting properties and reproductive toxicity. However, the mechanisms under the reproductive disruptions are still not well understood. In this study, we explored the effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and possible mechanisms in mouse Leydig tumor cells (mLTC-1). Our results showed that BDE-47 could reduce progesterone production and decrease the intracellular cAMP level induced by hCG or forskolin. These suggested that BDE-47 decreasing progesterone production in mLTC-1 cells may be associated with the decline of intracellular cAMP level. Moreover, our data also indicated that the site G protein in cAMP-PKA pathway may be involved in this process. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse the decrease of progesterone biosynthesis, indicating that a post-cAMP site (or sites) might be involved into the BDE-47-decreased progesterone production. In addition, we found BDE-47 reduced the activity of P450 side chain cleavage enzyme (P450scc), which was companied with the decline of P450scc mRNA and protein level in mLTC-1 cells. Put all together, these results suggested that progesterone synthesis decrease induced by BDE-47 may be associated with attenuation of cAMP generation and reduction of P450scc activity.
@article{han_2244-tetrabromodiphenyl_2012,
	title = {2,2',4,4'-{Tetrabromodiphenyl} ether ({BDE}-47) decreases progesterone synthesis through {cAMP}-{PKA} pathway and {P}450scc downregulation in mouse {Leydig} tumor cells.},
	volume = {302},
	issn = {1879-3185},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/22867812},
	doi = {10.1016/j.tox.2012.07.010},
	abstract = {Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants in textiles, plastics and electronics and represent a group of persistent environmental contaminants. They have been found to accumulate in human and marine mammals. Previous studies have shown that PBDEs have endocrine-disrupting properties and reproductive toxicity. However, the mechanisms under the reproductive disruptions are still not well understood. In this study, we explored the effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on progesterone biosynthesis and possible mechanisms in mouse Leydig tumor cells (mLTC-1). Our results showed that BDE-47 could reduce progesterone production and decrease the intracellular cAMP level induced by hCG or forskolin. These suggested that BDE-47 decreasing progesterone production in mLTC-1 cells may be associated with the decline of intracellular cAMP level. Moreover, our data also indicated that the site G protein in cAMP-PKA pathway may be involved in this process. Furthermore, the addition of cAMP analog, 8-Br-cAMP, could not reverse the decrease of progesterone biosynthesis, indicating that a post-cAMP site (or sites) might be involved into the BDE-47-decreased progesterone production. In addition, we found BDE-47 reduced the activity of P450 side chain cleavage enzyme (P450scc), which was companied with the decline of P450scc mRNA and protein level in mLTC-1 cells. Put all together, these results suggested that progesterone synthesis decrease induced by BDE-47 may be associated with attenuation of cAMP generation and reduction of P450scc activity.},
	number = {1},
	journal = {Toxicology},
	author = {Han, Xiumei and Tang, Rong and Chen, Xiaojiao and Xu, Bo and Qin, Yufeng and Wu, Wei and Hu, Yanhui and Xu, Bin and Song, Ling and Xia, Yankai and Wang, Xinru},
	month = dec,
	year = {2012},
	pmid = {22867812},
	keywords = {Animals, Cholesterol Side-Chain Cleavage Enzyme, Cholesterol Side-Chain Cleavage Enzyme: genetics, Cholesterol Side-Chain Cleavage Enzyme: metabolism, Chorionic Gonadotropin, Chorionic Gonadotropin: pharmacology, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Cyclic AMP-Dependent Protein Kinases: metabolism, Cyclic AMP: metabolism, Down-Regulation, Down-Regulation: drug effects, Flame retardants, Forskolin, Forskolin: pharmacology, Gene Expression Regulation, Humans, Leydig Cell Tumor, Messenger, Messenger: metabolism, Mice, Neoplastic, Neoplastic: drug effec, Polybrominated Biphenyls, Polybrominated Biphenyls: toxicity, Progesterone, Progesterone: biosynthesis, RNA, Tumor, cell line},
	pages = {44--50}
}

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