ECE2017 Eposter Presentations: Interdisciplinary Endocrinology Endocrine Disruptors (5 abstracts)
Identification of chemicals disrupting adrenal steroid production by steroid profiling in H295R cells
Petra Strajhar 1 , David Tonoli 2 , Fabienne Jeanneret 2 , Raphaella Imhof 1 , Vanessa Malagnino 1 , Melanie Patt 1 , Denise Kratschmar 1 , Julien Boccard 2 , Serge Rudaz 2 & Alex Odermatt 1
1University of Basel, Basel, Switzerland; 2University of Geneva, Geneva, Switzerland.
Human adrenal H295R cells are applied according to the validated OECD test guideline 456 to identify potential endocrine disrupting chemicals. Testosterone and estradiol production serves as read-out although these are not steroids typically produced by the adrenals. The current study attempted to optimize conditions for using H295R cells to detect chemicals disturbing the synthesis of key adrenal steroids. Culture supernatants of H295R cells were analysed by LC-MS-based steroid quantification. The impact of experimental conditions including time and serum content on steroid profiles was assessed. Steroid profiles were measured before and after incubation with reference and test compounds for potential disruption of adrenal steroidogenesis. The results revealed that H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amounts of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48 h incubation. Therefore, inclusion of positive and negative controls and a steroid profile of the complete medium prior to the experiment was needed to characterize steroid synthesis and indicate changes occurring upon exposure to chemicals. Among the test chemicals, octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the positive control torcetrapib. Gene expression analysis revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression; however, less pronounced compared with torcetrapib. In conclusion, the extended profiling and appropriate controls allow detecting chemicals that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chemicals for further investigations.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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