{"doi":"10.1530/acta.0.0760703","title":"SITES OF METYRAPONE INHIBITION OF STEROID BIOSYNTHESIS BY RAT ADRENAL MITOCHONDRIA","abstract":"<jats:title>ABSTRACT</jats:title>\n        <jats:p>Rat adrenal mitochondrial preparations supplemented with an NADPH-generating system were incubated with various labelled substrates in order to evaluate further the action of metyrapone on the utilization of cholesterol for steroid biosynthesis<jats:sup>1</jats:sup>). The formation of pregnenolone from [4-<jats:sup>14</jats:sup>C] cholesterol (0.5, 1.0 and 2.0 μCi) in 5, 10 and 15 min incubations was decreased by 72–82 % in the presence of metyrapone (0.5 m<jats:sc>m</jats:sc>). Similarly, the generation of labelled side chain fragments from [26-<jats:sup>14</jats:sup>C]-cholesterol was depressed 36–42 % by 0.2 m<jats:sc>m</jats:sc> metyrapone and 65–70 % by 1.0 m<jats:sc>m</jats:sc> inhibitor during 30, 60 and 90 min incubations. Metyrapone inhibition of the side chain cleavage was not observed, however, if cholesterol was replaced as substrate by its C-20 hydroxylated analog: The formation of pregnenolone from [7-<jats:sup>3</jats:sup>H]20α-hydroxycholesterol (0.5, 1.0 and 2.0 μCi), also an NADPH-mediated mitochondrial reaction, was not affected by similar concentrations of metyrapone, indicating that the inhibition observed with cholesterol as substrate is not related to non-specific toxic effects, to interference with NADPH generation or to impairment of NADPH function in the mitochondrial electron transport system. Parallel incubations with [4-<jats:sup>14</jats:sup>C] 11-deoxycorticosterone and with [4-<jats:sup>14</jats:sup>C] cholesterol over a wide range of inhibitor concentrations (0.01–1.0 m<jats:sc>m</jats:sc>) demonstrated that the effects of metyrapone on 11β-hydroxylation and on the side chain cleavage were dose-related; at low concentrations, however, metyrapone was a more potent inhibitor of 11β-hydroxylation than of cholesterol conversion to pregnenolone. These studies demonstrate clearly in the rat adrenal the dual inhibitory effect of metyrapone sug-gested by previous <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> observations in man.</jats:p>","journal":"Acta Endocrinologica","year":1974,"id":35966,"datarank":1.1083428829784434,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.6747871192940187,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.6747871192940187,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":11,"citers_with_citation_signal":11,"citers_with_endowment":11,"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":183104,"name":"Su Chiau Cheng","orcid":null,"position":1,"is_corresponding":false},{"id":183105,"name":"Lawrence M. Fishman","orcid":null,"position":2,"is_corresponding":false},{"id":183103,"name":"Andres Carballeira","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"4152546","pmcid":null,"openalex_id":"https://openalex.org/W2143149830","authors":[],"funders":[],"total_grants":0,"fwci":1.0572,"citation_percentile":0.76777328,"influential_citations":0,"citation_trend":[{"year":2017,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://eje.bioscientifica.com/view/journals/eje/76/4/acta_76_4_004.xml","host_type":"publisher"},{"url":"https://doi.org/10.1530/acta.0.0760703","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/4152546","host_type":"repository"}],"fields_of_study":["Hormonal Regulation and Hypertension","Estrogen and related hormone effects","Steroid Chemistry and Biochemistry","Medicine","Biology","Adrenal Glands","Animals","Carbon Radioisotopes","Cholesterol","Chromatography, Paper","Chromatography, Thin Layer","Depression, Chemical","Desoxycorticosterone","Dose-Response Relationship, Drug","Glucose-6-Phosphatase","Hydroxylation","Male","Metyrapone","Mitochondria","NADH, NADPH Oxidoreductases","Pregnenolone","Rats","Receptors, Drug","Time Factors","Tritium"],"mesh_terms":["Adrenal Glands","Animals","Carbon Radioisotopes","Cholesterol","Chromatography, Paper","Chromatography, Thin Layer","Depression, Chemical","Desoxycorticosterone","Dose-Response Relationship, Drug","Glucose-6-Phosphatase","Hydroxylation","Male","Metyrapone","Mitochondria","NADH, NADPH Oxidoreductases","Pregnenolone","Receptors, Drug","Time Factors","Tritium","Rats"],"keywords":["Metyrapone","Pregnenolone","Endocrinology","Internal medicine","Aminoglutethimide","Chemistry","Steroid","Cholesterol side-chain cleavage enzyme","Hydroxylation","Cholesterol","Mitochondrion","Biochemistry","Metabolism","Biology","Enzyme","Medicine","Cytochrome P450","Hormone"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T12:36:11.706613Z","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":[]}