Conservation of a Growth Hormone-Responsive Promoter Element in the Human and Mouse Acid-Labile Subunit Genes1

During extrauterine life, insulin-like growth factors (IGFs) circulate in a ternary serum complex with one IGF-binding protein-3 (IGFBP-3) or IGFBP-5 protein and with a single acid-labile subunit (ALS). GH increases levels of this ternary complex; in mice, this effect is achieved in part by the ability of GH to stimulate mouse ALS (mALS) transcription through an interferon-γ-activated sequence-like element (GLE) in the mALS promoter. To begin studying how GH regulates human ALS (hALS) gene expression, we cloned the hALS gene and found that it spans approximately 3.3 kb of DNA at chromosomal region 16p13.3. The hALS gene has two exons separated by a 1235-bp intron, which is found at the identical site in rat and mouse ALS genes. Sequence analysis reveals that the hALS 5′-flanking sequence is homologous to the mALS promoter, and that the GH-responsive GLE in the mALS promoter is conserved in both sequence and location in the hALS gene. The region spanning from −755 to −4 bp 5′ to the hALS ATG translation st...