{"doi":"10.1016/j.toxlet.2025.08.014","title":"Establishing scientific confidence in a two-chamber co-culture system to evaluate androgenic response in the presence of hepatic metabolism","abstract":"For the in vitro determination of toxicity on target organs in the presence of physiologically relevant human metabolism, we recently developed a two-chamber liver-target organ co-culture system in a medium-throughput 96-well format. Our proof-of-concept study using human HepaRG microtissues cultured in three-dimension (3D) and AR-CALUX reporter cells demonstrated the significantly reduced testosterone (T)-mediated androgen receptor (AR) responses in the presence of human liver metabolism. The present study further increased the scientific confidence in this two-chamber co-culture system as a flexible and robust tool to capture androgen-mediated responses by incorporating alternate AR reporter cell systems as the target and examining additional androgenic compounds. The system generated concordant metabolism-dependent changes in T- and 5α-dihydrotestosterone (DHT)-mediated AR responses using two different AR reporter cell systems (AR-CALUX, AR-INDIGO). The AR reporters had different sensitivity ranges and required media optimization. We demonstrated that this two-chamber co-culture system with integrated hepatic biotransformation can be used to evaluate endocrine activity with potential metabolism modulation of parent compounds.","journal":"Toxicology Letters","year":2025,"id":573876,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1292737,"name":"Susan J. Hall","orcid":"0000-0001-6738-5054","position":1,"is_corresponding":false},{"id":1130802,"name":"Samantha J. Madnick","orcid":"0000-0003-3631-0556","position":2,"is_corresponding":false},{"id":720324,"name":"Blanche C. Ip","orcid":"0000-0003-0063-5535","position":3,"is_corresponding":false},{"id":1252565,"name":"Paul L. Carmichael","orcid":"0000-0003-1353-9032","position":4,"is_corresponding":false},{"id":1480988,"name":"Hequn Li","orcid":"0000-0002-5529-9236","position":5,"is_corresponding":false},{"id":1480989,"name":"Wei Chen","orcid":"0009-0001-5743-8287","position":6,"is_corresponding":false},{"id":1293241,"name":"Lori A. Breitweiser","orcid":null,"position":7,"is_corresponding":false},{"id":1293242,"name":"Heather E. Pence","orcid":null,"position":8,"is_corresponding":false},{"id":1481405,"name":"David M. Ames","orcid":null,"position":9,"is_corresponding":false},{"id":1293243,"name":"Andrew J. Bowling","orcid":null,"position":10,"is_corresponding":false},{"id":353072,"name":"Kamin J. Johnson","orcid":"0000-0003-4550-5566","position":11,"is_corresponding":false},{"id":1292739,"name":"Richard Cubberley","orcid":"0000-0002-5464-0068","position":12,"is_corresponding":false},{"id":1481406,"name":"Bruce A. Sherf","orcid":null,"position":13,"is_corresponding":false},{"id":720326,"name":"Jeffrey R. Morgan","orcid":"0000-0002-7546-3443","position":14,"is_corresponding":false},{"id":755952,"name":"Kim Boekelheide","orcid":"0000-0003-4564-8057","position":15,"is_corresponding":false},{"id":1292736,"name":"Tessa C.A. van Tongeren","orcid":"0000-0002-6068-485X","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:36.753600Z","pmid":"40902835","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}