{"corpus_id":17326149,"paper_sha":"9c184fe77b492f859e85ab503a5bae8c5ecee4e9","doi":"10.1677/JME.0.0220045","arxiv_id":null,"pmid":9924179,"pmcid":null,"mag_id":1974635112,"dblp_id":null,"acl_id":null,"title":"GnRH agonist treatment decreases progesterone synthesis, luteal peripheral benzodiazepine receptor mRNA, ligand binding and steroidogenic acute regulatory protein expression during pregnancy.","year":1999,"publication_date":"1999-02-01","venue":"Journal of Molecular Endocrinology","journal":{"name":"Journal of molecular endocrinology","pages":"\n          45-54\n        ","volume":"22 1"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Biology","Medicine"],"reference_count":38,"citation_count":55,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"3-Hydroxysteroid Dehydrogenases","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D015096"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Biological Transport","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D001692"},{"d":"Cholesterol","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002784"},{"d":"Cholesterol Side-Chain Cleavage Enzyme","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D002786"},{"d":"Corpus Luteum","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D003338"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Gene Expression Regulation","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D005786"},{"d":"Gonadotropin-Releasing Hormone","mj":false,"qs":[{"q":"agonists","mj":true,"ui":"Q000819"},{"q":"analogs & derivatives","mj":true,"ui":"Q000031"},{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D007987"},{"d":"Mitochondria","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"},{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008928"},{"d":"Phosphoproteins","mj":false,"qs":[{"q":"biosynthesis","mj":true,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D010750"},{"d":"Phosphorylation","mj":false,"ui":"D010766"},{"d":"Pregnancy","mj":false,"ui":"D011247"},{"d":"Pregnancy, Animal","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D011270"},{"d":"Progesterone","mj":false,"qs":[{"q":"biosynthesis","mj":true,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D011374"},{"d":"RNA, Messenger","mj":false,"qs":[{"q":"biosynthesis","mj":false,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D012333"},{"d":"Rats","mj":false,"ui":"D051381"},{"d":"Rats, Sprague-Dawley","mj":false,"ui":"D017207"},{"d":"Receptors, GABA-A","mj":false,"qs":[{"q":"biosynthesis","mj":true,"ui":"Q000096"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D011963"},{"d":"Steroidogenic Acute Regulatory Protein","mj":false,"ui":"D000098682"}],"chemicals":[{"n":"Phosphoproteins","ui":"D010750","reg":"0"},{"n":"RNA, Messenger","ui":"D012333","reg":"0"},{"n":"Receptors, GABA-A","ui":"D011963","reg":"0"},{"n":"Steroidogenic Acute Regulatory Protein","ui":"D000098682","reg":"0"},{"n":"Gonadotropin-Releasing Hormone","ui":"D007987","reg":"33515-09-2"},{"n":"Progesterone","ui":"D011374","reg":"4G7DS2Q64Y"},{"n":"Cholesterol","ui":"D002784","reg":"97C5T2UQ7J"},{"n":"3-Hydroxysteroid Dehydrogenases","ui":"D015096","reg":"EC 1.1.-"},{"n":"Cholesterol Side-Chain Cleavage Enzyme","ui":"D002786","reg":"EC 1.14.15.6"},{"n":"lutrelin acetate","ui":"C030741","reg":"G137G5DMW7"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"We have demonstrated that continuous administration of a gonadotropin-releasing hormone agonist (GnRH-Ag) suppresses luteal steroidogenesis in the pregnant rat. We further demonstrated that the peripheral-type benzodiazepine receptor (PBR) and the steroidogenic acute regulatory protein (StAR) play key roles in cholesterol transport leading to steroidogenesis. The purpose of this study was to understand the cellular and molecular mechanisms involved in the suppression of luteal steroidogenesis leading to a fall in serum progesterone levels in GnRH-Ag-treated rats during early pregnancy. Pregnant rats were treated individually starting on day 8 of pregnancy with 5 microgram/day GnRH-Ag using an osmotic minipump. Sham-operated control rats received no treatment. At 0, 4, 8 and 24 h after initiation of the treatment, rats were killed and corpora lutea (CL) were removed for PBR mRNA, protein and radioligand binding analyses, immunoblot 1-D gel analysis of StAR, P450 scc and 3beta-hydroxysteroid dehydrogenase as well as 2-D gel analysis of StAR. The treatment decreased the luteal PBR mRNA expression at all time periods starting at 4 h compared with that in corresponding sham controls. GnRH-Ag also reduced, in the CL, the PBR protein/ligand binding, the StAR protein and P450 scc protein and its activity as early as 8 h after the treatment and they remained low compared with those in corresponding sham controls. The data from 2-D gel studies suggest that the majority of the decrease in StAR protein appears to be in the phosphorylated forms of StAR. Thus, we have demonstrated, for the first time, the presence of PBR and StAR in the pregnant rat CL and that the coordinated suppression of these proteins involved in the mitochondrial cholesterol transport along with P450 scc by GnRH-Ag leads to reduced ovarian steroidogenesis.","claims":[{"public_id":"cl_d6e6208731dcc081426f487d8a397509","status":"active","text":"GnRH agonist treatment also reduces P450 scc protein and activity in the corpora lutea, and these levels remain low relative to sham controls.","confidence":0.96,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_d6e6208731dcc081426f487d8a397509"},{"public_id":"cl_4b2b0a57577acbb2e8c4774bb44ef18c","status":"active","text":"GnRH agonist treatment decreases luteal peripheral benzodiazepine receptor mRNA expression beginning 4 h after treatment and lowers peripheral benzodiazepine receptor protein/ligand binding by 8 h.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_4b2b0a57577acbb2e8c4774bb44ef18c"},{"public_id":"cl_df5c0dc8eb55fd8b8eb6deee89ba46f9","status":"active","text":"GnRH agonist treatment reduces steroidogenic acute regulatory protein abundance, with the main decrease occurring in phosphorylated forms of steroidogenic acute regulatory protein.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_df5c0dc8eb55fd8b8eb6deee89ba46f9"},{"public_id":"cl_abe237f6e8ba73f94c7a52b2f897e3a0","status":"active","text":"GnRH agonist treatment suppresses luteal steroidogenesis in pregnant rats, leading to reduced serum progesterone during early pregnancy.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_abe237f6e8ba73f94c7a52b2f897e3a0"},{"public_id":"cl_f7ea4d357f437af19f85a9d44aac5dee","status":"active","text":"Peripheral-type benzodiazepine receptor and steroidogenic acute regulatory protein are present in pregnant rat corpora lutea, and their coordinated suppression with P450 scc is linked to reduced ovarian steroidogenesis.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_f7ea4d357f437af19f85a9d44aac5dee"}],"concepts":[{"public_id":"co_04292a09c1e2232097dcfed1fadd838e","status":"active","name":"steroidogenic acute regulatory protein","description":"A protein that facilitates cholesterol transport 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serum.","types":["biomarker","hormone"],"aliases":["progesterone levels"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0bca2adcd8207f33b2448962e258dbb8"},{"public_id":"co_0cccd7848e70560014609957625c98f8","status":"active","name":"luteal steroidogenesis","description":"Steroid hormone synthesis by the corpus luteum during pregnancy.","types":["biological process"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0cccd7848e70560014609957625c98f8"},{"public_id":"co_0e6b971d1e7c2fb32f363b03ecf98c7e","status":"active","name":"PBR mRNA","description":"Messenger RNA encoding the peripheral-type benzodiazepine receptor.","types":["molecular measurement"],"aliases":["peripheral-type benzodiazepine receptor mRNA"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0e6b971d1e7c2fb32f363b03ecf98c7e"},{"public_id":"co_19579f3bff7e8ce9923f7cf77a90a057","status":"active","name":"gonadotropin-releasing hormone agonist","description":"A synthetic agonist of gonadotropin-releasing hormone used here to treat pregnant rats continuously.","types":["compound","treatment"],"aliases":["GnRH-Ag"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_19579f3bff7e8ce9923f7cf77a90a057"},{"public_id":"co_32925024b89f5db7a5f4403b1eb59999","status":"active","name":"phosphorylated forms of StAR","description":"Post-translationally modified forms of steroidogenic acute regulatory protein carrying phosphate 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