{"doi":"10.1530/acta.0.0760689","title":"METABOLISM OF [4-14C]CHOLESTEROL BY HUMAN ADRENAL GLANDS IN VITRO AND ITS INHIBITION BY METYRAPONE","abstract":"<jats:title>ABSTRACT</jats:title>\n        <jats:p>The <jats:italic>in vitro</jats:italic> conversion of [4-<jats:sup>14</jats:sup>C] cholesterol<jats:sup>1</jats:sup>) to steroid hormones was studied in 1 normal, 1 adenomatous and 2 hyperplastic, surgically resected, human adrenals. The degree of overall conversion per gram of tissue was similar (4.4–5.6 %) in NADPH-supplemented homogenates from normal or moderately hyperactive adrenals; a 2-fold increase was found in a markedly hyperfunctioning gland. Only labelled cortisol, corticosterone, 11-deoxycortisol, 11-deoxycorticosterone and androstenedione were isolated from incubations with [4-<jats:sup>14</jats:sup>C] cholesterol, but cortisol accounted for slightly more than 50 % of overall substrate conversion in the normal adrenal, while 11-deoxycortisol and androstenedione predominated in the abnormal glands. \"Apparent 11β-hydroxylase activity\" was considerably lower in the abnormal glands than in normal tissue when assessed using [4-<jats:sup>14</jats:sup>C] cholesterol as substrate, but this deficit was not observed in comparable incubations with <jats:sup>14</jats:sup>C-labelled pregnenolone, progesterone or 11-deoxycorticosterone. [4-<jats:sup>14</jats:sup>C] Cholesterol was a more efficient precursor of androstenedione than either [4-<jats:sup>14</jats:sup>C] pregnenolone or [4-<jats:sup>14</jats:sup>C] progesterone.</jats:p>\n        <jats:p>In parallel studies, metyrapone (1.0 m<jats:sc>m</jats:sc>) depressed the formation of both 11-oxy and 11-deoxymetabolies from [4-<jats:sup>14</jats:sup>C] cholesterol, overall inhibition ranging from 66 to 86%. The conversion of [4-<jats:sup>14</jats:sup>C] 11-deoxycorticosterone to corticosterone was inhibited by 93 % under identical conditions. Metyrapone did not, however, impair the overall transformation of either [4-<jats:sup>14</jats:sup>C]pregnenolone or [4-<jats:sup>14</jats:sup>C]progesterone, since the inhibition of cortisol and corticosterone biosynthesis was associated with an increment in 11-deoxycortisol (with [4-<jats:sup>14</jats:sup>C] pregnenolone) or 11-deoxycorticosterone (with [4-<jats:sup>14</jats:sup>C]progesterone). From these studies it appears likely that the additional site of metyrapone inhibition of steroid biosynthesis suggested by others on the basis of clinical observations involves the rate-limiting, ACTH-regulated conversion of cholesterol to pregnenolone.</jats:p>","journal":"Acta Endocrinologica","year":1974,"id":36071,"datarank":0.551501268185607,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.17876527071740683,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.17876527071740683,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":5,"citers_with_citation_signal":4,"citers_with_endowment":4,"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":2.4849066497880004,"endowment":2.4849066497880004,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"4407893","pmcid":null,"openalex_id":"https://openalex.org/W2104139840","authors":[],"funders":[],"total_grants":0,"fwci":1.0572,"citation_percentile":0.7648583,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://eje.bioscientifica.com/view/journals/eje/76/4/acta_76_4_003.xml","host_type":"publisher"},{"url":"https://doi.org/10.1530/acta.0.0760689","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/4407893","host_type":"repository"}],"fields_of_study":["Hormonal Regulation and Hypertension","Steroid Chemistry and Biochemistry","Hormonal and reproductive studies","Medicine","17-Hydroxycorticosteroids","Adenoma","Adrenal Gland Diseases","Adrenal Gland Neoplasms","Adrenal Glands","Adrenalectomy","Adrenocortical Hyperfunction","Adult","Androstenedione","Carbon Radioisotopes","Cholesterol","Chromatography, Paper","Chromatography, Thin Layer","Corticosterone","Depression, Chemical","Desoxycorticosterone","Female","Humans","Hydrocortisone","In Vitro Techniques","Metyrapone","Middle Aged","Pregnenolone","Progesterone","Tritium"],"mesh_terms":["Adenoma","Adrenal Gland Diseases","Adrenocortical Hyperfunction","Adrenal Gland Neoplasms","Adrenal Glands","Adrenalectomy","Adult","Androstenedione","Carbon Radioisotopes","Cholesterol","Chromatography, Paper","Chromatography, Thin Layer","Corticosterone","Depression, Chemical","Desoxycorticosterone","Female","Humans","Hydrocortisone","Metyrapone","Middle Aged","Pregnenolone","Progesterone","Tritium","17-Hydroxycorticosteroids","In Vitro Techniques"],"keywords":["Pregnenolone","Internal medicine","Endocrinology","Metyrapone","Androstenedione","Corticosterone","Chemistry","Cholesterol","In vitro","Steroid","Metabolism","Hormone","Biology","Medicine","Biochemistry","Androgen"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T14:08:49.065493Z","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":[]}