1. Structural bisphenol analoques differentially target steroidogenesis in murine MA-10 Leydig cells as well as the glucocorticoid receptor
- Author
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Roelofs, Maarke J, van den Berg, Martin, Bovee, Toine F H, Piersma, Aldert H, van Duursen, Majorie B, Sub IRAS Tox CMT/ETX, LS IRAS Tox Algemeen, LS IRAS Tox RTX (Reprod.en ontw.toxic.), Risk Assessment of Toxic and Immunomodulatory Agents, IRAS RATIA1, Sub IRAS Tox CMT/ETX, LS IRAS Tox Algemeen, LS IRAS Tox RTX (Reprod.en ontw.toxic.), Risk Assessment of Toxic and Immunomodulatory Agents, and IRAS RATIA1
- Subjects
Male ,Novel Foods & Agrochains ,Bisphenol ,Gene Expression ,Endocrine Disruptors ,Toxicology ,Novel Foods & Agroketens ,brominated flame retardants ,Mice ,chemistry.chemical_compound ,Glucocorticoid receptor ,Yeasts ,tetrabromobisphenol-a tbbpa ,Testis ,Testosterone ,exogenous progesterone ,Sulfones ,BU Toxicology, Novel Foods & Agrochains ,Receptor ,Cells, Cultured ,Leydig cell ,AFSG Quality in Chains ,BU Toxicology ,Leydig Cells ,medicine.anatomical_structure ,BU Toxicologie, Novel Foods & Agroketens ,Receptors, Androgen ,Tetrabromobisphenol A ,Biological Assay ,hormones, hormone substitutes, and hormone antagonists ,medicine.medical_specialty ,endocrine system ,Cell Survival ,BU Toxicologie ,Polybrominated Biphenyls ,united-states ,in-vitro ,Receptors, Glucocorticoid ,Phenols ,Internal medicine ,medicine ,Animals ,Benzhydryl Compounds ,endocrine-disrupting chemicals ,urogenital system ,Cholesterol side-chain cleavage enzyme ,risk-assessment ,fetal testis ,gene-expression ,Androgen receptor ,Endocrinology ,chemistry ,Bisphenol S ,one-generation reproduction - Abstract
Although much information on the endocrine activity of bisphenol A (BPA) is available, a proper human hazard assessment of analogues that are believed to have a less harmful toxicity profile is lacking. Here the possible effects of BPA, bisphenol F (BPF), bisphenol S (BPS), as well as the brominated structural analogue and widely used flame retardant tetrabromobisphenol A (TBBPA) on human glucocorticoid and androgen receptor (GR and AR) activation were assessed. BPA, BPF, and TBBPA showed clear GR and AR antagonism with IC50 values of 67 μM, 60 μM, and 22 nM for GR, and 39 μM, 20 μM, and 982 nM for AR, respectively, whereas BPS did not affect receptor activity. In addition, murine MA-10 Leydig cells exposed to the bisphenol analogues were assessed for changes in secreted steroid hormone levels. Testicular steroidogenesis was altered by all bisphenol analogues tested. TBBPA effects were more directed towards the male end products and induced testosterone synthesis, while BPF and BPS predominantly increased the levels of progestagens that are formed in the beginning of the steroidogenic pathway. The MA-10 Leydig cell assay shows added value over the widely used H295R steroidogenesis assay because of its fetal-like characteristics and specificity for the physiologically more relevant testicular Δ4 steroidogenic pathway. Therefore, adding an in vitro assay covering fetal testicular steroidogenesis, such as the MA-10 cell line, to the panel of tests used to screen potential endocrine disruptors, is highly recommendable.
- Published
- 2015