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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3-Hydroxysteroid Dehydrogenases / metabolism
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Antigens, Polyomavirus Transforming / genetics*
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Antigens, Polyomavirus Transforming / physiology
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Cell Line, Transformed
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Cholesterol Side-Chain Cleavage Enzyme / genetics
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Chorionic Gonadotropin / metabolism
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Chorionic Gonadotropin / pharmacology
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Cyclic AMP / analysis
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Humans
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Hyperplasia
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Inhibins*
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Leydig Cell Tumor / etiology*
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Leydig Cell Tumor / pathology
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Leydig Cell Tumor / physiopathology
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Leydig Cells / pathology
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Luteinizing Hormone / metabolism
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Male
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Mice
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Mice, Transgenic
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Peptides / genetics*
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Progesterone / analysis
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Promoter Regions, Genetic / genetics*
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RNA, Messenger / analysis
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Receptors, LH / analysis
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Receptors, LH / genetics
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Simian virus 40 / immunology*
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Testicular Neoplasms / etiology
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Testicular Neoplasms / pathology
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Testosterone / analysis
Substances
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Antigens, Polyomavirus Transforming
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Chorionic Gonadotropin
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Peptides
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RNA, Messenger
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Receptors, LH
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inhibin-alpha subunit
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8-Bromo Cyclic Adenosine Monophosphate
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Testosterone
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Progesterone
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Inhibins
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Luteinizing Hormone
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Cyclic AMP
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3-Hydroxysteroid Dehydrogenases
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Cholesterol Side-Chain Cleavage Enzyme