Journal article
Hydroxylated and sulfated metabolites of commonly occurring airborne polychlorinated biphenyls inhibit human steroid sulfotransferases SULT1E1 and SULT2A1
Environmental toxicology and pharmacology, Vol.58, pp.196-201
03/2018
DOI: 10.1016/j.etap.2018.01.010
PMCID: PMC6078096
PMID: 29408762
Abstract
•Hydroxylated metabolites of airborne PCBs inhibited steroid sulfotransferases.•SULT1E1 and SULT2A1 differed in their specificities for OH-PCBs as inhibitors.•The corresponding PCB sulfates were either not inhibitory or were weak inhibitors.•Metabolites of these PCBs have the potential to affect steroid hormone signaling.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that are associated with varied adverse health effects. Lower chlorinated PCBs are prevalent in indoor and outdoor air and can be metabolized to their hydroxylated derivatives (OH-PCBs) followed by sulfation to form PCB sulfates. Sulfation is also a means of signal termination for steroid hormones. The human estrogen sulfotransferase (SULT1E1) and alcohol/hydroxysteroid sulfotransferase (SULT2A1) catalyze the formation of steroid sulfates that are inactive at steroid hormone receptors. We investigated the inhibition of SULT1E1 (IC50s ranging from 7.2 nM to greater than 10 μM) and SULT2A1 (IC50s from 1.3 μM to over 100 μM) by five lower-chlorinated OH-PCBs and their corresponding PCB sulfates relevant to airborne PCB-exposure. Several congeners of lower chlorinated OH-PCBs relevant to airborne PCB exposures were potent inhibitors of SULT1E1 and SULT2A1 and thus have the potential to disrupt regulation of intracellular concentrations of the receptor-active steroid substrates for these enzymes.
Details
- Title: Subtitle
- Hydroxylated and sulfated metabolites of commonly occurring airborne polychlorinated biphenyls inhibit human steroid sulfotransferases SULT1E1 and SULT2A1
- Creators
- Victoria S Parker - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, United StatesEdwin J Squirewell - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, United StatesHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, United StatesLarry W Robertson - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, IA, United StatesMichael W Duffel - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA, United States
- Resource Type
- Journal article
- Publication Details
- Environmental toxicology and pharmacology, Vol.58, pp.196-201
- DOI
- 10.1016/j.etap.2018.01.010
- PMID
- 29408762
- PMCID
- PMC6078096
- NLM abbreviation
- Environ Toxicol Pharmacol
- ISSN
- 1382-6689
- eISSN
- 1872-7077
- Publisher
- Elsevier B.V
- Language
- English
- Date published
- 03/2018
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984000920302771
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