US EPA

698232 

Journal Article 

Effects of endocrine disruptors on dehydroepiandrosterone sulfotransferase and enzymes involved in PAPS synthesis: genomic and nongenomic pathways 

Harris, R; Turan, N; Kirk, C; Ramsden, D; Waring, R 

2007 

Yes 

Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 

US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE 

RES TRIANGLE PK 

115, Suppl. 1 

SUPPL1 

51-54 

English 

18174950 

10.1289/ehp.9365 

WOS:000207172600008 

https://ehp.niehs.nih.gov/doi/10.1289/ehp.9365
Exit
 

Background
Sulfation plays an important role both in detoxification and in the control of steroid activity. Studies in rodents have shown that the conversion of dehydroepiandrosterone (DHEA) to DHEA-sulfate is involved in learning and the memory process.

Methods
The effects of a range of plasticizers and related compounds commonly encountered in the environment were evaluated kinetically against human DHEA sulfotransferase (SULT 2A1) and by reverse transcriptase-polymerase chain reaction (RT-PCR) against several enzymes involved in the synthesis of the sulfotransferase cofactor adenosine 3′-phosphate 5′-phosphosulfate (PAPS).

Results
We found that several of the chemicals acted as competitive inhibitors of SULT 2A1 (Ki for 4-tert-octylphenol is 2.8 μM). Additionally, after treatment of TE 671 cells with 0.005–0.5 μM 4-n-octylphenol, bis(2-ethylhexyl)phthalate, and diisodecyl phthalate, real-time RT-PCR showed dose-dependent decreases in the steady-state mRNA levels of cysteine dioxygenase type I, sulfite oxidase, and 3′-phosphate 5′-phosphosulfate synthase I.

Conclusions
These data suggest that environmental contaminants may exert effects on neuronal function both by direct inhibition of sulfotransferase enzymes and by interrupting the supply of PAPS, which has wider implications for endocrine disruption and xenobiotic metabolism. 

Endocrine Disruptors; Environmental Pollutants; Multienzyme Complexes; Phenols; Phthalic Acids; Plasticizers; RNA, Messenger; Phosphoadenosine Phosphosulfate; 482-67-7; 4-octylphenol; 7DF2B8LH3P; Diethylhexyl Phthalate; C42K0PH13C; Cysteine Dioxygenase; EC 1.13.11.20; Sulfite Oxidase; EC 1.8.3.1; PAPS synthetase; EC 2.7.7.4; Sulfate Adenylyltransferase; Sulfotransferases; EC 2.8.2.-; dehydroepiandrosterone sulfotransferase; diisodecyl phthalate; WF93T741QI; Index Medicus; nongenomic; endocrine disruptor; sulfotransferase; Sulfate Adenylyltransferase -- metabolism; Phthalic Acids -- toxicity; Plasticizers -- toxicity; Sulfate Adenylyltransferase -- drug effects; Reverse Transcriptase Polymerase Chain Reaction; Cysteine Dioxygenase -- drug effects; Multienzyme Complexes -- drug effects; Dose-Response Relationship, Drug; RNA, Messenger -- metabolism; Sulfite Oxidase -- drug effects; Multienzyme Complexes -- metabolism; Cysteine Dioxygenase -- metabolism; Diethylhexyl Phthalate -- toxicity; Phenols -- toxicity; RNA, Messenger -- drug effects; Cell Line, Tumor; Medulloblastoma -- metabolism; Sulfite Oxidase -- metabolism; Endocrine Disruptors -- toxicity; Sulfotransferases -- drug effects; Phosphoadenosine Phosphosulfate -- metabolism; Environmental Pollutants -- toxicity; Sulfotransferases -- metabolism