THE THYROID-HORMONE DOWN-REGULATES THE MOUSE ALPHA-FETOPROTEIN PROMOTER

The thyroid hormone (T3) was shown to down regulate the level of alpha -foetoprotein (AFP) mRNA in hepatoma cells HepG2. Recombinant plasmids containing segments from the mouse AFP gene promoter were transfected in HepG2 cells and transient expression assays showed that the T3 inh ibitory effect depends on the sequence limited by positions -80 and -3 8, upstream from the TATA box. This sequence is able to confer T3 sens itivity to a heterologous promoter and contains a putative T3-responsi ve element, as well as likely CEBP- and HNF1-responsive elements. Thes e observations suggest that T3 is a good candidate for hormonal contro l of the AFP gene expression and especially for the neonatal shut off of the gene. (C) 1997 Elsevier Science Ireland Ltd.