THYROID-HORMONE REGULATION OF ALPHA-MYOSIN HEAVY-CHAIN PROMOTER ACTIVITY ASSESSED BY INVIVO DNA TRANSFER IN RAT-HEART

We have studied the thyroid-hormone responsiveness of the alpha-myosin heavy chain (MHC) gene in, vivo by directly injecting an expression vector containing the alpha-MHC 5′ regulatory sequences (-613 to +421 base pairs) into the rat heart. In the expression vector pAM1Luc the alpha-MHC promoter elements direct the synthesis of firefly luciferase. Although thyroxine administration of both euthyroid and thyroidectomized rats for 5 days increased alpha-MHC promoter activity, the pAM1Luc gene construct did not mimic expression of the endogenous gene. These studies of direct gene transfer into mammalian myocardium suggest that additional cis-acting elements necessary for the in, vivo response to thyroid hormone reside outside the -613 to +421 region. © 1991.