Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line Export

@article{citeulike:6083411, abstract = {Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo . However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17β and modulation of nine major enzyme genes involved in the synthesis of steroid hormones ( CYP11A , CYP11B1 , CYP17 , CYP19 , 17βHSD1 , 17βHSD4 , CYP21 , 3βHSD2 , StAR ) in human adrenal H295R cells supplied with cAMP. Exposure to 10 − 7 to 10 − 5  M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17β levels and increased progesterone secretion. At 10 − 5  M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17βHSD4 and significantly suppressed expression of 3βHSD2 . In comparison, 10 − 7 to 2 × 10 − 5  M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17β, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19 . Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols.}, author = {Furuta, C. and Noda, S. and Li, C. and Suzuki, A. and Taneda, S. and Watanabe, G. and Taya, K.}, citeulike-article-id = {6083411}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.taap.2008.01.026}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0041008X08000549}, day = {15}, doi = {10.1016/j.taap.2008.01.026}, issn = {0041008X}, journal = {Toxicology and Applied Pharmacology}, keywords = {adrenals, cortisol, detoxification, diesel, disruption, estrogenic, exhaust, genes, hormone, nitrophenols, pollution, thyroid}, month = {May}, number = {1}, pages = {109--120}, posted-at = {2009-11-07 22:52:14}, priority = {2}, title = {Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line}, url = {http://dx.doi.org/10.1016/j.taap.2008.01.026}, volume = {229}, year = {2008} }

TY - JOUR ID - citeulike:6083411 L3 - citeulike-article-id:6083411 N2 - Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4-nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo and that PNMC accumulate in adrenal glands in vivo . However, the impacts of exposure to these compounds on adrenal endocrine disruption and steroidogenesis have not been investigated. To elucidate the non-receptor mediated effects of PNMC and PNMPP, we investigated the production of the steroid hormones progesterone, cortisol, testosterone, and estradiol-17β and modulation of nine major enzyme genes involved in the synthesis of steroid hormones ( CYP11A , CYP11B1 , CYP17 , CYP19 , 17βHSD1 , 17βHSD4 , CYP21 , 3βHSD2 , StAR ) in human adrenal H295R cells supplied with cAMP. Exposure to 10 − 7 to 10 − 5  M PNMC and 1 mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17β levels and increased progesterone secretion. At 10 − 5  M, PNMC with 1 mM 8-Br-cAMP significantly stimulated expression of the 17βHSD4 and significantly suppressed expression of 3βHSD2 . In comparison, 10 − 7 to 2 × 10 − 5  M PNMPP with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17β, increased progesterone levels, but did not affect testosterone and cortisol secretion due to the significant suppression of CYP17 and the non-significant but obvious suppression of CYP19 . Our results clarified steroidogenic enzymes as candidates responsible for the inhibition or stimulation for the production of steroid hormones in the steroidogenic pathway, thus providing the first experimental evidence for multiple mechanisms of disruption of endocrine pathways by these nitrophenols. IS - 1 JF - Toxicology and Applied Pharmacology SN - 0041008X EP - 120 TI - Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene expression and steroid synthesis in the human H295R adrenocortical cell line VL - 229 SP - 109 KW - adrenals KW - cortisol KW - detoxification KW - diesel KW - disruption KW - estrogenic KW - exhaust KW - genes KW - hormone KW - nitrophenols KW - pollution KW - thyroid AU - Furuta, C AU - Noda, S AU - Li, C AU - Suzuki, A AU - Taneda, S AU - Watanabe, G AU - Taya, K PY - 2008/05/15/ UR - http://dx.doi.org/10.1016/j.taap.2008.01.026 ER -