The present studies were undertaken to evaluate the utility of the H295R system as an in vitro assay to assess the potential of chemicals to modulate steroidogenesis. The effects of four model chemicals on the expression of ten steroidogenic genes and on the production of three steroid hormones were examined. Exposures with individual model chemicals as well as binary mixtures were conducted. Although the responses reflect the known mode of action of the various compounds, the results show that designating a chemical as "specific inducer or inhibitor" is unwise. Not all changes in the mixture exposures could be predicted based on results from individual chemical exposures. Hormone production was not always directly related to gene expression. The H295R system integrates the effects of direct-acting hormone agonists and antagonists as well as chemicals affecting signal transduction pathways for steroid production and provides data on both gene expression and hormone secretion which makes this cell line a valuable tool to examine effects of chemicals on steroidogenesis.
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http://dx.doi.org/10.1016/j.ecoenv.2006.06.012 | DOI Listing |
Surgery
January 2025
Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Champaign, IL; Department of Surgery, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Champaign, IL. Electronic address:
Background: Recent multigenomic analysis of adrenocortical carcinomas (ACCs) identified SLC7A11/xCT as a novel biomarker. The Food and Drug Administration-approved anti-inflammatory drug, sulfasalazine (SAS), induces ferroptosis by blocking SLC7A11 expression. We hypothesize that SAS could be repurposed to target ACC cells.
View Article and Find Full Text PDFFront Pharmacol
August 2024
Swiss Centre for Applied Human Toxicology (SCAHT), University of Basel, Basel, Switzerland.
The triazole antifungals posaconazole and itraconazole can cause pseudohyperaldosteronism with hypertension and hypokalemia, edema, and gynecomastia by inhibiting steroid synthesis and metabolism. Mechanisms underlying pseudohyperaldosteronism include inhibition of adrenal 11β-hydroxylase cytochrome-P450 (CYP) 11B1 and 17α-hydroxylase (CYP17A1) as well as peripherally expressed 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). To enhance specificity for fungal CYP51, tetrazoles have been developed.
View Article and Find Full Text PDFEnviron Pollut
September 2024
Institut National de la Recherche Scientifique (INRS), Centre Armand Frappier Santé Biotechnologie, Laval, QC, Canada. Electronic address:
Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development.
View Article and Find Full Text PDFJ Steroid Biochem Mol Biol
October 2024
Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Bern University Hospital, University of Bern, Switzerland; Department for BioMedical Research, Bern University Hospital, University of Bern, Switzerland. Electronic address:
Int J Mol Sci
February 2024
National Institutes of Health Clinical Center, 10 Center Drive, Bethesda, MD 20892, USA.
Adrenal myelolipomas (AML) are composed of mature adipose and hematopoietic components. They represent approximately 3 percent of adrenal tumors and are commonly found in patients with congenital adrenal hyperplasia (CAH). CAH provides a unique environment to explore AML pathogenesis.
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