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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
Author(s) -
Sánchez-Pacheco Aurora,
Peña Pilar,
Palomino Teresa,
Güell Ana,
Castrillo José Luis,
Aranda Ana
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01609-8
Subject(s) - retinoic acid , receptor , transcription factor , endocrinology , alternative splicing , medicine , biology , gene isoform , thyroid hormone receptor , retinoic acid receptor , retinoic acid inducible orphan g protein coupled receptor , hormone , chemistry , microbiology and biotechnology , gene , biochemistry
The rat growth hormone (GH) promoter was significantly activated in non‐pituitary cells by the expression of unliganded trioodothyronine (T3) and retinoic acid (RA) receptors. Furthermore, a strong ligand‐dependent activation was found in the presence of the pituitary‐specific transcription factor GHF‐1. When compared with GHF‐1, the splice variant GHF‐2 showed a decreased ability to bind the cognate site in the GH promoter. As a consequence, expression of GHF‐2 had little stimulatory effect on the GH promoter and did not show cooperation with T3 or RA receptors even in the presence of ligands. Furthermore, over‐expression of GHF‐2 inhibited the response to T3 and RA in pituitary cells. These results show that alternative splicing of the GHF‐1 gene gives rise to two isoforms that differ in their transactivating properties and in their ability to synergize with the nuclear thyroid hormone and retinoic acid receptors on GH gene expression.