Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis.
Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10(-5) M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10(-7) M and CYP11B2 at 10(-9) M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis.
Li
Lih-Ann
LA
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 35053, Taiwan, ROC. lihann@nhri.org.tw
Lin
Tsu-Chun Emma
TC
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D012333:RNA, Messenger; D000450:Aldosterone; D011374:Progesterone; D011189:Potassium Chloride; D019326:17-alpha-Hydroxyprogesterone; D011078:Polychlorinated Biphenyls; D008156:Luciferases; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; C023035:3,4,5,3',4'-pentachlorobiphenyl; D006854:Hydrocortisone