EXPRESSION OF A THYROID HORMONE-RESPONSIVE RECOMBINANT GENE INTRODUCED INTO ADULT MICE LIVERS BY REPLICATION-DEFECTIVE ADENOVIRUS CAN BE REGULATED BY ENDOGENOUS THYROID-HORMONE RECEPTOR

We constructed a recombinant adenovirus carrying the firefly luciferas e gene driven by the thymidine kinase promoter and controlled by the p alindromic thyroid hormone/retinoic acid-responsive element. The same adenovirus vector without the hormone-responsive element was used as c ontrol. Regulation of the luciferase gene expression was tested in pit uitary-derived GH cells and hepatoma-derived HepG2 cells infected with the recombinant adenoviruses. Administration of triiodothyronine to G H cells and all-trans-retinoic acid to HepG2 cells resulted in 8.0 +/- 0.3-fold and 4.6 +/- 0.5-fold induction of luciferase activity, respe ctively. No significant increase was observed with the control adenovi rus. Hormonal regulation was also examined in adult mice. Mice deplete d of thyroid hormone were injected intravenously with the recombinant adenoviruses and given 4 times the replacement dose of triiodothyronin e or vehicle only for 4 days. Hormone administration resulted in 4.2-f old increase of luciferase activity in liver homogenates, No significa nt effect was observed in animals injected with the control adenovirus . This recombinant adenovirus provides a new experimental system in th e study of thyroid hormone and retinoic acid action and offers the pot ential to regulate by physiological means the expression of genes tran sferred for the purpose of therapy.