THE TRANSCRIPTION FACTOR GHF-1, BUT NOT THE SPLICE VARIANT GHF-2, COOPERATES WITH THYROID-HORMONE AND RETINOIC ACID RECEPTORS TO STIMULATE RAT GROWTH-HORMONE GENE-EXPRESSION

The rat growth hormone (GH) promoter was significantly activated in no n-pituitary cells by the expression of unliganded trioodothyronine (T3 ) and retinoic acid (RA) receptors, Furthermore, a strong ligand-depen dent activation was found in the presence of the pituitary-specific tr anscription factor GHF-1, When compared with GHF-1, the splice variant GHF-2 shelved a decreased ability to bind the cognate site in the GH promoter, iis a consequence, expression of GHF-2 had little stimulator y effect on the GH promoter and did not show cooperation with T3 or RA receptors even in the presence of ligands, Furthermore, over-expressi on of GHF-2 inhibited the response to T3 and RA in pituitary cells, Th ese results show that alternative splicing of the GHF-1 gene gives ris e to two isoforms that differ in their transactivating properties and in their ability to synergize, with the nuclear thyroid hormone and re tinoic acid receptors on GH gene expression. (C) 1998 Federation of Eu ropean Biochemical Societies.