title: Low-dose Bisphenol A Activates Cyp11a1 Gene Expression and Corticosterone Secretion in Adrenal Gland via the JNK Signaling Pathway.
abstract: Certain commonly used compounds that interfere with the functions of the endocrine system are classified as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA) is an EDC that is widely used in food containers. BPA levels in human sera are commonly observed to be approximately 1-100 nM. Compared with the effects of BPA on the gonads, its effects on the adrenal gland are poorly understood. To investigate the influence of BPA on steroidogenesis, we examined the activity of the steroidogenic gene Cyp11a1 and its regulatory pathways in mouse Y1 adrenal cortex cells. Treatment with BPA at < 100 µM did not cause cell death. However, increased promoter activity and protein expression of Cyp11a1 were induced by low doses of BPA (10-1000 nM). Moreover, BPA induced c-Jun phosphorylation, and a specific inhibitor of c-Jun N-terminal kinase (JNK) significantly suppressed BPA-induced steroidogenesis. Thus, treatment of adrenal cells with low doses of BPA activated Cyp11a1 and increased corticosterone production through the JNK/c-Jun signaling pathway. Identical results were observed in rats after BPA injection. The abnormal induction of hormone synthesis by BPA in the adrenal gland might be linked to human metabolic defects and neuropsychiatric disorders.
authors.affiliation: Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan blue2010@mail.ndmctsgh.edu.tw.
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Lan
authors.affiliation: Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Lin
authors.affiliation: Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jyun-Hong
authors.initials: JH
authors.lastname: Lin
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001559:Benzhydryl Compounds / Q000097:blood / Q000633:toxicity*; D045744:Cell Line, Tumor; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000819:agonists* / Q000097:blood / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism; D052244:Endocrine Disruptors / Q000097:blood / Q000633:toxicity*; D004785:Environmental Pollutants / Q000097:blood / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D010636:Phenols / Q000097:blood / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000819:agonists / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D066007:Toxicokinetics; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003345:Corticosterone; D000242:Cyclic AMP; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D048031:JNK Mitogen-Activated Protein Kinases; D010636:Phenols; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Cyp11a1; adrenal gland; bisphenol A (BPA); c-Jun; corticosterone