THE MOUSE INHIBIN ALPHA-SUBUNIT PROMOTER DIRECTS SV40 T-ANTIGEN TO LEYDIG-CELLS IN TRANSGENIC MICE

Testicular tumorigenesis was observed in transgenic mice expressing th e 6-kb mouse inhibin cr-subunit promoter/Simian virus 40 T-antigen (SV 40 Tag) fusion gene. The tumors were confined to Leydig cells using im munohistochemistry with anti-Tag antibody, specific binding of biotiny lated 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, res pectively. An immortalized cell line, BLT-1, was established from one testicular tumor. These cells expressed the LH receptor and P450soc mR NAs, and displayed LH-responsive cAMP and progesterone production, and low testosterone production. The cells also specifically bound I-125- labeled recombinant human LK with high affinity (36 000 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.