title: Effects and mechanisms of nonylphenol on corticosterone release in rat zona fasciculata-reticularis cells.
abstract: Alkylphenol ethoxylate, consisting of ∼80% nonylphenol ethoxylate (NPEO), is a major group of nonionic surfactant. The primary degradation product of NPEO, nonylphenol (NP), interferes with reproduction, induces cell death in gonads, and leads to changes in other reproductive parameters. With such apparent stress, NP is believed to induce stress response mechanism, i.e., adrenal cortical hormone. However, the effects and action mechanisms of NP on rat adrenal zona fasciculata-reticularis (ZFR) cells are still unclear. This study explored the effects of NP on corticosterone release. ZFR cells were incubated with NP in the presence or absence of adrenocorticotropin (ACTH), 8-bromo-cyclic 3',5'-adenosine monophosphate (8-Br-cAMP), forskolin (FSK), 25-hydroxyl cholesterol (25-OH-cholesterol), pregnenolone, progesterone, or deoxycorticosterone at 37°C for 1 h. The concentrations of corticosterone or pregnenolone in the spent media were measured by radioimmunoassay. The expressions of steroidogenic acute regulatory (StAR) protein, cytochrome P450 side-chain cleavage (P450scc) protein, and 11β-hydroxylase in the cells were measured by Western blot. The data demonstrated that (1) NP stimulated corticosterone release induced by ACTH, 8-Br-cAMP, FSK, 25-OH-cholesterol, pregnenolone, progesterone, or deoxycorticosterone; (2) NP significantly increased pregnenolone release in the control, 25-OH-cholesterol, trilostane, and 25-OH-cholesterol + trilostane groups; (3) NP-stimulated corticosterone release was estrogen receptor dependent, but mediated by nitric oxide and p38 mitogen-activated protein kinase pathway independent; and (4) NP did not affect StAR, 11β-hydroxylase, or P450scc protein expression. These results suggest that NP acts directly on rat ZFR cells to stimulate corticosterone release and that the stimulation mechanism of NP mediates through post-cAMP corticosterone manufacture enzymes, i.e., P450scc and 11β-hydroxylase.
authors.affiliation: Department of Chemical and Materials Engineering, Chinese Culture University, Shih-Lin, Taipei 11114, Taiwan, Republic of China. llchiang@staff.pccu.edu.tw
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chang
authors.forename: Wan-Song
authors.initials: WS
authors.lastname: Alfred Wun
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006888:Hydroxycholesterols / Q000494:pharmacology; D008297:Male; D010636:Phenols / Q000633:toxicity*; D010750:Phosphoproteins / Q000378:metabolism; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D015383:Zona Fasciculata / Q000187:drug effects* / Q000378:metabolism; D015385:Zona Reticularis / Q000187:drug effects* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006888:Hydroxycholesterols; D010636:Phenols; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003900:Desoxycorticosterone; D011374:Progesterone; D011284:Pregnenolone; C007997:25-hydroxycholesterol; C025256:nonylphenol; D000324:Adrenocorticotropic Hormone; D013252:Steroid 11-beta-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone