{"doi":"10.1002/jcb.10738","title":"Antisteroidogenic actions of hydrogen peroxide on rat leydig cells","abstract":"<jats:title>Abstract</jats:title><jats:p>It has been well known that reactive oxygen species (ROS) are produced in the steroidogenic pathway and spermatozoa. H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub>, one of ROS produced by spermatozoa, appears to be a primary toxic agent. In the present study, we examined the effects of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> on the basal and evoked‐testosterone release from primary Leydig cells, the protein expressions of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were also investigated. Our preparation was found to contain approximately 87% Leydig cells and very few macrophages. The results demonstrated that H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> (&gt;1 × 10<jats:sup>−4</jats:sup> M) significantly inhibited the basal and hCG‐stimulated testosterone release. H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> abolished forskolin‐ or 8‐Br‐cAMP‐evoked testosterone release. In the presence of pregnenolone, progesterone, or androstenedione, the inhibitory effect of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> on testosterone release was prevented. H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> also inhibited pregnenolone production in the presence of trilostane (an inhibitor of 3β‐hydroxysteroid dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In addition to the inhibition of hormone secretion, H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> also regulated steroidogenesis by diminishing protein expression of StAR. These results suggest that H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450scc activity and StAR protein expression. © 2003 Wiley‐Liss, Inc.</jats:p>","journal":"Journal of Cellular Biochemistry","year":2003,"id":36991,"datarank":3.4644783023503782,"base_score":4.356708826689592,"endowment":4.356708826689592,"self_citation_contribution":0.6535063240034389,"citation_network_contribution":2.8109719783469393,"self_endowment_contribution":0.6535063240034389,"citer_contribution":2.8109719783469393,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":75,"citers_with_citation_signal":65,"citers_with_endowment":65,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":186261,"name":"Chien‐Chen Lu","orcid":null,"position":1,"is_corresponding":false},{"id":186262,"name":"Chiu‐Shuang Lin","orcid":null,"position":2,"is_corresponding":false},{"id":186191,"name":"Paulus S. Wang","orcid":null,"position":3,"is_corresponding":false},{"id":186260,"name":"Shiow‐Chwen Tsai","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.356708826689592,"endowment":4.356708826689592,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"14635199","pmcid":null,"openalex_id":"https://openalex.org/W2081337319","authors":[],"funders":[],"total_grants":0,"fwci":0.8517,"citation_percentile":0.74485166,"influential_citations":1,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":5},{"year":2016,"count":8},{"year":2018,"count":5},{"year":2019,"count":4},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":7},{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcb.10738","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcb.10738","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/jcb.10738","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcb.10738","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcb.10738","host_type":"publisher"},{"url":"https://doi.org/10.1002/jcb.10738","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14635199","host_type":"repository"}],"fields_of_study":["Hormonal and reproductive studies","Sperm and Testicular Function","Stress Responses and Cortisol","Biology","Medicine","8-Bromo Cyclic Adenosine Monophosphate","Androstenedione","Animals","Cholesterol Side-Chain Cleavage Enzyme","Colforsin","Dihydrotestosterone","Dose-Response Relationship, Drug","Enzyme Inhibitors","Hydrogen Peroxide","Hydroxycholesterols","Leydig Cells","Male","Oxidants","Phosphoproteins","Pregnenolone","Progesterone","Rats","Rats, Sprague-Dawley","Spermatozoa","Testosterone","Steroidogenic Acute Regulatory Protein"],"mesh_terms":["Steroidogenic Acute Regulatory Protein","Androstenedione","Animals","Cholesterol Side-Chain Cleavage Enzyme","Dose-Response Relationship, Drug","Enzyme Inhibitors","Colforsin","Hydrogen Peroxide","Hydroxycholesterols","Leydig Cells","Male","Phosphoproteins","Pregnenolone","Progesterone","Spermatozoa","Dihydrotestosterone","Testosterone","8-Bromo Cyclic Adenosine Monophosphate","Oxidants","Rats, Sprague-Dawley","Rats"],"keywords":["Cholesterol side-chain cleavage enzyme","Pregnenolone","Steroidogenic acute regulatory protein","Leydig cell","Internal medicine","Endocrinology","Testosterone (patch)","Chemistry","Forskolin","Reactive oxygen species","Androstenedione","Hormone","Cytochrome P450","Biology","Steroid","Androgen","Metabolism","Biochemistry","Gene expression","Luteinizing hormone","Stimulation","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T18:03:21.690915Z","pmid":null,"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":[]}