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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.
AuthorsK Kananen, M Markkula, T el-Hefnawy, F P Zhang, T Paukku, J G Su, A J Hsueh, I Huhtaniemi
JournalMolecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 119 Issue 2 Pg. 135-46 (May 31 1996) ISSN: 0303-7207 [Print] Ireland
PMID8807633 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antigens, Polyomavirus Transforming
  • Chorionic Gonadotropin
  • Peptides
  • RNA, Messenger
  • Receptors, LH
  • inhibin-alpha subunit
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Testosterone
  • Progesterone
  • Inhibins
  • Luteinizing Hormone
  • Cyclic AMP
  • 3-Hydroxysteroid Dehydrogenases
  • Cholesterol Side-Chain Cleavage Enzyme
Topics
  • 3-Hydroxysteroid Dehydrogenases (metabolism)
  • 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
  • Animals
  • Antigens, Polyomavirus Transforming (genetics, physiology)
  • Cell Line, Transformed
  • Cholesterol Side-Chain Cleavage Enzyme (genetics)
  • Chorionic Gonadotropin (metabolism, pharmacology)
  • Cyclic AMP (analysis)
  • Humans
  • Hyperplasia
  • Inhibins
  • Leydig Cell Tumor (etiology, pathology, physiopathology)
  • Leydig Cells (pathology)
  • Luteinizing Hormone (metabolism)
  • Male
  • Mice
  • Mice, Transgenic
  • Peptides (genetics)
  • Progesterone (analysis)
  • Promoter Regions, Genetic (genetics)
  • RNA, Messenger (analysis)
  • Receptors, LH (analysis, genetics)
  • Simian virus 40 (immunology)
  • Testicular Neoplasms (etiology, pathology)
  • Testosterone (analysis)

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