title: The mouse inhibin alpha-subunit promoter directs SV40 T-antigen to Leydig cells in transgenic mice.
abstract: Testicular tumorigenesis was observed in transgenic mice expressing the 6-kb mouse inhibin alpha-subunit promoter/Simian virus 40 T-antigen (SV40 Tag) fusion gene. The tumors were confined to Leydig cells using immunohistochemistry with anti-Tag antibody, specific binding of biotinylated hCG and histochemistry for 3 beta-hydroxysteroid dehydrogenase. Leydig cell hyperplasia and presence of Tag protein in the testicular interstitial tissue were already evident at 5 and 6.5 days of age, respectively. An immortalized cell line, BLT-1, was established from one testicular tumor. These cells expressed the LH receptor and P450scc mRNAs, and displayed LH-responsive cAMP and progesterone production, and low testosterone production. The cells also specifically bound 125I-labeled recombinant human LH with high affinity (36000 binding sites/cell), and the binding was regulated by 8Br-cAMP and hCG. This gonadal tumor model is valuable for further studies on endocrine functions of Leydig cells and their tumorigenesis in vivo and in vitro.
authors.affiliation: Department of Physiology, University of Turku, Finland. kirsi.kananen@utu.fi
authors.forename: K
authors.initials: K
authors.lastname: Kananen
authors.forename: M
authors.initials: M
authors.lastname: Markkula
authors.forename: T
authors.initials: T
authors.lastname: el-Hefnawy
authors.forename: F P
authors.initials: FP
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Paukku
authors.forename: J G
authors.initials: JG
authors.lastname: Su
authors.forename: A J
authors.initials: AJ
authors.lastname: Hsueh
authors.forename: I
authors.initials: I
authors.lastname: Huhtaniemi
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000502:physiology; D002461:Cell Line, Transformed; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D006801:Humans; D006965:Hyperplasia; D007265:Inhibins; D007984:Leydig Cell Tumor / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007985:Leydig Cells / Q000473:pathology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000235:genetics*; D011374:Progesterone / Q000032:analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D011974:Receptors, LH / Q000032:analysis / Q000235:genetics; D013539:Simian virus 40 / Q000276:immunology*; D013736:Testicular Neoplasms / Q000209:etiology / Q000473:pathology; D013739:Testosterone / Q000032:analysis
chemical_list: D000952:Antigens, Polyomavirus Transforming; D006063:Chorionic Gonadotropin; D010455:Peptides; D012333:RNA, Messenger; D011974:Receptors, LH; C094377:inhibin-alpha subunit; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D011374:Progesterone; D007265:Inhibins; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme