title: Estrone sulfate and dehydroepiandrosterone sulfate: Transactivation of the estrogen and androgen receptor.
abstract: Dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E1S) are two of the most abundant steroids in the human circulation. The enzyme steroid sulfatase (STS) cleaves the sulfate group of DHEAS and E1S leading to biosynthesis of endogenous hormones such as testosterone and estrone. In the current study we aimed at determining the effect of E1S and DHEAS on estrogen receptor (ER) and androgen receptor (AR) transactivation. Using luciferase reporter gene assays, the ER and AR transactivities of E1S and DHEAS were determined by direct cell exposure; as well as upon extraction from human serum using a method to extract perfluorinated alkyl acids (PFAAs). By direct cell exposure, both E1S and DHEAS transactivated the ER and the AR in dose-dependent manners. The DHEAS-induced AR transactivity could be abolished by the STS inhibitor STX64. Immunoassay analysis confirmed the presence of E1S and DHEAS in the serum PFAA extracts with mean recoveries below 2.5%. For the PFAA extracts of human male and female serum, only the AR was significantly transactivated. The AR transactivity of the sulfated steroids in the extracts was abolished by STX64 to obtain the net PFAA induced xenohormone transactivity, but further cleanup might be needed at high concentrations of E1S.
authors.affiliation: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Allé 2, Build. 1260, DK-8000 Aarhus C, Denmark. Electronic address: cbjr@ph.au.dk.
authors.forename: Christian
authors.initials: C
authors.lastname: Bjerregaard-Olesen
authors.affiliation: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Allé 2, Build. 1260, DK-8000 Aarhus C, Denmark.
authors.forename: Mandana
authors.initials: M
authors.lastname: Ghisari
authors.affiliation: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Allé 2, Build. 1260, DK-8000 Aarhus C, Denmark.
authors.forename: Lisbeth S
authors.initials: LS
authors.lastname: Kjeldsen
authors.affiliation: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Allé 2, Build. 1260, DK-8000 Aarhus C, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Wielsøe
authors.affiliation: Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department of Public Health, Aarhus University, Bartholins Allé 2, Build. 1260, DK-8000 Aarhus C, Denmark.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Bonefeld-Jørgensen
mesh_terms: D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005466:Fluorocarbons / Q000737:chemistry; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects* / Q000235:genetics
chemical_list: C410798:AR protein, human; D004967:Estrogens; D005466:Fluorocarbons; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D004970:Estrone; D019314:Dehydroepiandrosterone Sulfate; C017296:estrone sulfate
keywords: Androgen receptor; Dehydroepiandrosterone sulfate; Estrogen receptor; Estrone sulfate; Perfluorinated compounds; Steroid sulfatase