Conservation of a growth hormone-responsive promoter element in the human and mouse acid-labile subunit genes

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 abil ity of GH to stimulate mouse ALS (mALS) transcription through an interferon -gamma-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 chromosoma l 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'-flanbing sequence is homologous to the m ALS promoter, and that the GH-responsive GLE in the mALS promoter is conser ved in both sequence and location in the hALS gene. The region spanning fro m -755 to -4 bp 5' to the hALS ATG translation start codon directs expressi on of a luciferase reporter gene in primary rat hepatocytes, and GH increas es reporter expression in the presence of the native, but not a mutant, GLE in the hALS promoter. These data suggest that GH stimulates hALS and mALS gene expression by a similar mechanism, which involves at least in part a c onserved GLE in the ALS promoter.