This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 2155

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Inhibition of Sulfotransferase E1 (SULT1E1)

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

SULT1E1 inhibition

Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Cell term
glandular cell of endometrium

Organ term

Organ term
uterus

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Process	Object	Action
sulfotransferase activity	estrogen sulfotransferase	decreased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
SULT1E1 inhibition and increased oestradiol availability	MolecularInitiatingEvent	Ana-Andreea Cioca (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Life stage	Evidence
Adult

Sex Applicability

An indication of the the relevant sex for this KE. More help

Term	Evidence
Mixed

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Both SULT1E1 expression and function can be measured in tissues and in recombinant systems, such as e.g., Salmonella typhimurium (Kester et al., 2002), Escherichia coli (Parker et al., 2018), V79-1E1 Chinese hamster cells line (Hamers et al., 2006) and in HepG2 cell (Maiti et al., 2007).

Expression (gene expression and proteins level)

qRT-PCRn, Northern blotting: SULT1E1 expression (Konings et al., 2018)
Western blotting: SULT1E1 protein levels (Konings et al., 2018)
Immunohistochemistry: protein levels (Konings et al., 2018)

Activity (formation of E2 sulfate)

Sulfotransferase kinetic assay: radiometric assays (Hempel et al., 2000; Falany et al., 1995)

In these assays, different types of inhibition of SULT activity, such as competitive, non-competitive and mixed type can be also determined by Lineweaver-Burk analysis (Kester et al., 2002; Hamers et al., 2006).

Levels of sulphated estrogens and/or ratio of conjugated E2/non conjugated E2 (in tissue or in plasma):
- liquid chromatography/mass spectrometry (LC/MS); LC-MS/MS after chemical or enzymatic hydrolysis and extraction (Borghoff et al., 2016, Wudy et al., 2018).
- Radioimmuno Assay (RIA)
Computational models for SULTE1 activation and such as QSAR model for E2-SULT inhibition are also used to demonstrate the criteria for potent inhibition of estrogen sulfotransferase (Harju et al., 2007; Gosavi et al., 2013).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

Taxonomic Applicability: Vertebrates and Invertebrates.

Life Stage applicability: all life stages; this AOP specifically refer to the adulthood

Sex Applicability: both sexes, this AOP specifically refer to the females

References

List of the literature that was cited for this KE description. More help

Biswas DK, Singh S, Shi Q, Pardee AB and Iglehart JD, 2005. Crossroads of estrogen receptor and NF-kappaB signaling. Sci STKE, 2005:pe27. doi: 10.1126/stke.2882005pe27

Borghoff SJ, Wikoff D, Harvey S and Haws L, 2016. Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3:190-201. doi: 10.1016/j.toxrep.2016.01.007

Britton DJ, Hutcheson IR, Knowlden JM, Barrow D, Giles M, McClelland RA, Gee JM and Nicholson RI, 2006. Bidirectional cross talk between ERalpha and EGFR signalling pathways regulates tamoxifen-resistant growth. Breast Cancer Res Treat, 96:131-146. doi: 10.1007/s10549-005-9070-2

Brooks SC, Rozhin J, Pack BA, Horn L, Godefroi VC, Locke ER, Zemlicka J and Singh DV, 1978. Role of sulfate conjugation in estrogen metabolism and activity. J Toxicol Environ Health, 4:283-300. doi: 10.1080/15287397809529662

Browne P, Judson RS, Casey WM, Kleinstreuer NC and Thomas RS, 2015. Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model. Environmental Science & Technology, 49:8804-8814. doi: 10.1021/acs.est.5b02641

Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F and Pasqualini JR, 2000. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol, 72:23-27. doi: 10.1016/s0960-0760(00)00040-6

Dao TL, Hayes C and Libby PR, 1974. Steroid Sulfatase Activities in Human Breast Tumors. Proceedings of the Society for Experimental Biology and Medicine, 146:381-384. doi: 10.3181/00379727-146-38109

Dubik D and Shiu RPC, 1992. Mechanism of estrogen activation of c-myc oncogene expression. Oncogene, 7 8:1587-1594

ECB, 2006 European Union Risk Assessment Report. 2,2’,6,6’-tetrabromo-4,4’-isopropylidenediphenol, (tetrabromobisphenol-A or TBBP-A). Part II – human health. Luxembourg: Office for Official Publications of the European Communities, European Commission – Joint Research Centre Institute for Health and Consumer Protection.

ECHA, 2006. 2,2’,6,6’-TETRABROMO-4,4’-ISOPROPYLIDENEDIPHENOL (TETRABROMOBISPHENOL-A or TBBP-A) Part II – human health United Kingdom, European Chemicals Agency.

Ellmann S, Sticht H, Thiel F, Beckmann MW, Strick R and Strissel PL, 2009. Estrogen and progesterone receptors: from molecular structures to clinical targets. Cell Mol Life Sci, 66:2405-2426. doi: 10.1007/s00018-009-0017-3

Falany JL, Azziz R and Falany CN, 1998. Identification and characterization of cytosolic sulfotransferases in normal human endometrium. Chem Biol Interact, 109:329-339. doi: 10.1016/s0009-2797(97)00143-9

Fox EM, Andrade J and Shupnik MA, 2009. Novel actions of estrogen to promote proliferation: integration of cytoplasmic and nuclear pathways. Steroids, 74:622-627. doi: 10.1016/j.steroids.2008.10.014

Gosavi RA, Knudsen GA, Birnbaum LS and Pedersen LC, 2013. Mimicking of estradiol binding by flame retardants and their metabolites: a crystallographic analysis. Environ Health Perspect, 121:1194-1199. doi: 10.1289/ehp.1306902

Gourdy P, Guillaume M, Fontaine C, Adlanmerini M, Montagner A, Laurell H, Lenfant F and Arnal J-F, 2018. Estrogen receptor subcellular localization and cardiometabolism. Molecular Metabolism, 15:56-69. doi: https://doi.org/10.1016/j.molmet.2018.05.009

Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Kester MH, Andersson PL, Legler J and Brouwer A, 2006. In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol Sci, 92:157-173. doi: 10.1093/toxsci/kfj187

Heldring N, Pike, A., Andersson, S., Matthews, J., Cheng, G., Hartman, J., Tujague, M., Ström, A., Treuter, E., Warner, M., & Gustafsson, J., 2007. Estrogen Receptors: How Do They Signal and What Are Their Targets. Physiological Reviews, 87:905–931

ISO, 2018a. ISO 19040-1:2018

Water quality — Determination of the estrogenic potential of water and waste water — Part 1: Yeast estrogen screen (Saccharomyces cerevisiae). Place.

ISO, 2018b. ISO 19040-2:2018

Water quality — Determination of the estrogenic potential of water and waste water — Part 2: Yeast estrogen screen (A-YES, Arxula adeninivorans). Place.

James MO, Li W, Summerlot DP, Rowland-Faux L and Wood CE, 2010. Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta. Environ Int, 36:942-949. doi: 10.1016/j.envint.2009.02.004

Jung EM, An BS, Choi KC and Jeung EB, 2012. Potential estrogenic activity of Triclosan in the uterus of immature rats and rat pituitary GH3 cells. Toxicol Lett, 208:142-148. doi: 10.1016/j.toxlet.2011.10.017

Kester MH, Bulduk S, van Toor H, Tibboel D, Meinl W, Glatt H, Falany CN, Coughtrie MW, Schuur AG, Brouwer A and Visser TJ, 2002. Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites of polyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J Clin Endocrinol Metab, 87:1142-1150. doi: 10.1210/jcem.87.3.8311

Konings G, Brentjens L, Delvoux B, Linnanen T, Cornel K, Koskimies P, Bongers M, Kruitwagen R, Xanthoulea S and Romano A, 2018. Intracrine Regulation of Estrogen and Other Sex Steroid Levels in Endometrium and Non-gynecological Tissues; Pathology, Physiology, and Drug Discovery. Frontiers in pharmacology, 9:940. Doi:10.3389/fphar.2018.00940. Available online: http://europepmc.org/abstract/MED/30283331

Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL and Manolagas SC, 2001. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell, 104:719-730

Li G, Zhang J, Jin K, He K, Zheng Y, Xu X, Wang H, Wang H, Li Z, Yu X, Teng X, Cao J and Teng L, 2013. Estrogen receptor-α36 is involved in development of acquired tamoxifen resistance via regulating the growth status switch in breast cancer cells. Mol Oncol, 7:611-624. doi: 10.1016/j.molonc.2013.02.001

Louis GW, Hallinger DR and Stoker TE, 2013. The effect of Triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat. Reprod Toxicol, 36:71-77. doi: 10.1016/j.reprotox.2012.12.001

Montagnini BG, Pernoncine KV, Borges LI, Costa NO, Moreira EG, Anselmo-Franci JA, Kiss ACI and Gerardin DCC, 2018. Investigation of the potential effects of Triclosan as an endocrine disruptor in female rats: Uterotrophic assay and two-generation study. Toxicology, 410:152-165. doi: 10.1016/j.tox.2018.10.005

Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Warner M and Gustafsson JA, 2001. Mechanisms of estrogen action. Physiol Rev, 81:1535-1565. doi: 10.1152/physrev.2001.81.4.1535

OECD, 2007. Test No. 440: Uterotrophic Bioassay in Rodents.

OECD, 2009. Test No. 230: 21-day Fish Assay.

OECD, 2012. Test No. 457: BG1Luc Estrogen Receptor Transactivation Test Method for Identifying Estrogen Receptor Agonists and Antagonists.

OECD, 2015a. Test No. 455: Performance-Based Test Guideline for Stably Transfected Transactivation In Vitro Assays to Detect Estrogen Receptor Agonists and Antagonists.

OECD, 2015b. Test No. 493: Performance-Based Test Guideline for Human Recombinant Estrogen Receptor (hrER) In Vitro Assays to Detect Chemicals with ER Binding Affinity.

OECD, 2018. Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption.

OECD, 2021. Test No. 250: EASZY assay - Detection of Endocrine Active Substances, acting through estrogen receptors, using transgenic tg(CYP19A1B:GFP) Zebrafish embrYos.

PACK BA and BROOKS SC, 1974. Cyclic Activity of Estrogen Sulfotransferase in the Gilt Uterus. Endocrinology, 95:1680-1690. doi: 10.1210/endo-95-6-1680

Pasqualini JR and Chetrite GS, 1999. Estrone sulfatase versus estrone sulfotransferase in human breast cancer: potential clinical applications. J Steroid Biochem Mol Biol, 69:287-292. doi: 10.1016/s0960-0760(99)00082-5

Pasqualini JR, Gelly C and Lecerf F, 1986. Biological effects and morphological responses to estriol, estriol-3-sulfate, estriol-17-sulfate and tamoxifen in a tamoxifen-resistant cell line (R-27) derived from MCF-7 human breast cancer cells. European Journal of Cancer and Clinical Oncology, 22:1495-1501. doi: 10.1016/0277-5379(86)90086-6

Pedram A, Razandi M, Blumberg B and Levin ER, 2016. Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content. Faseb j, 30:230-240. doi: 10.1096/fj.15-274878

Pedram A, Razandi M, Lewis M, Hammes S and Levin ER, 2014. Membrane-localized estrogen receptor α is required for normal organ development and function. Dev Cell, 29:482-490. doi: 10.1016/j.devcel.2014.04.016

Qian YM, Sun XJ, Tong MH, Li XP, Richa J and Song W-C, 2001. Targeted Disruption of the Mouse Estrogen Sulfotransferase Gene Reveals a Role of Estrogen Metabolism in Intracrine and Paracrine Estrogen Regulation. Endocrinology, 142:5342-5350. doi: 10.1210/endo.142.12.8540

Reinen J and Vermeulen NP, 2015. Biotransformation of endocrine disrupting compounds by selected phase I and phase II enzymes--formation of estrogenic and chemically reactive metabolites by cytochromes P450 and sulfotransferases. Curr Med Chem, 22:500-527. doi: 10.2174/0929867321666140916123022

Rodríguez PE and Sanchez MS, 2010. Maternal exposure to Triclosan impairs thyroid homeostasis and female pubertal development in Wistar rat offspring. J Toxicol Environ Health A, 73:1678-1688. doi: 10.1080/15287394.2010.516241

Sanders JM, Coulter SJ, Knudsen GA, Dunnick JK, Kissling GE and Birnbaum LS, 2016. Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicology and Applied Pharmacology, 298:31-39. doi: https://doi.org/10.1016/j.taap.2016.03.007

Shevtsov S, Petrotchenko EV, Pedersen LC and Negishi M, 2003. Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase. Environ Health Perspect, 111:884-888. doi: 10.1289/ehp.6056

Shupnik MA, 2004. Crosstalk between steroid receptors and the c-Src-receptor tyrosine kinase pathways: implications for cell proliferation. Oncogene, 23:7979-7989. doi: 10.1038/sj.onc.1208076

Sinreih M, Knific T, Anko M, Hevir N, Vouk K, Jerin A, Frković Grazio S and Rižner TL, 2017. The Significance of the Sulfatase Pathway for Local Estrogen Formation in Endometrial Cancer. Frontiers in pharmacology, 8. doi: 10.3389/fphar.2017.00368

Stoker TE, Gibson EK and Zorrilla LM, 2010. Triclosan exposure modulates estrogen-dependent responses in the female wistar rat. Toxicol Sci, 117:45-53. doi: 10.1093/toxsci/kfq180

Tong MH, Jiang H, Liu P, Lawson JA, Brass LF and Song WC, 2005. Spontaneous fetal loss caused by placental thrombosis in estrogen sulfotransferase-deficient mice. Nat Med, 11:153-159. doi: 10.1038/nm1184

USEPA, 2009. Endocrine disruptor screening program test guidelines OPPTS 890.1250: estrogen receptor binding (rat uterine cytosol). . EPA (ed.). Washington DC.

Utsunomiya H, Ito K, Suzuki T, Kitamura T, Kaneko C, Nakata T, Niikura H, Okamura K, Yaegashi N and Sasano H, 2004. Steroid sulfatase and estrogen sulfotransferase in human endometrial carcinoma. Clin Cancer Res, 10:5850-5856. doi: 10.1158/1078-0432.Ccr-04-0040

Wang LQ and James MO, 2006. Inhibition of sulfotransferases by xenobiotics. Curr Drug Metab, 7:83-104. doi: 10.2174/138920006774832596

Wilson VS, Bobseine K and Gray LE, Jr., 2004. Development and Characterization of a Cell Line That Stably Expresses an Estrogen-Responsive Luciferase Reporter for the Detection of Estrogen Receptor Agonist and Antagonists. Toxicological Sciences, 81:69-77. doi: 10.1093/toxsci/kfh180

Yang J, Singleton DW, Shaughnessy EA and Khan SA, 2008. The F-domain of estrogen receptor-alpha inhibits ligand induced receptor dimerization. Mol Cell Endocrinol, 295:94-100. doi: 10.1016/j.mce.2008.08.001

Zheng A, Kallio A and Härkönen P, 2007. Tamoxifen-induced rapid death of MCF-7 breast cancer cells is mediated via extracellularly signal-regulated kinase signaling and can be abrogated by estrogen. Endocrinology, 148:2764-2777. doi: 10.1210/en.2006-1269