Abstract
GH and PRL stimulate both proliferation and insulin production in pancreatic beta-cells as well as in the rat insulinoma cell line RIN-5AH, We report here that human GH increases insulin mRNA levels in RIN-5AH cells via both somatogenic and lactogenic receptors. GH stimulated the rat insulin 1 promoter activity 2-fold, and this stimulation was abolished by introduction of a block mutation in a gamma-interferon-activated sequence (GAS)-like element (GLE) with the sequence 5'-TTCTGGGAA-3' located in the rat insulin 1 enhancer at position -330 to -322. This element, termed Ins-GLE, was able to confer GH responsiveness to a heterologous promoter. GH induced the binding of two protein complexes to the Ins-GLE. An antibody directed against the transcription factor STAT5 (signal transducer and activator of transcription) supershifted the GH-induced complexes. Furthermore, in COS7 cells transiently transfected with STAT5 and GH receptor cDNAs, it was found that expression of STAT5 was necessary for GH induction of these two DNA-binding complexes. These results suggest that GH stimulates insulin 1 promoter activity by inducing the binding of STAT5 to Ins-GLE.
| Original language | English |
|---|---|
| Journal | Molecular endocrinology (Baltimore, Md.) |
| Volume | 10 |
| Issue number | 6 |
| Pages (from-to) | 652-60 |
| Number of pages | 9 |
| ISSN | 0888-8809 |
| Publication status | Published - Jun 1996 |
Keywords
- Animals
- Binding Sites
- DNA-Binding Proteins
- Gene Expression Regulation, Neoplastic
- Growth Hormone
- Insulin
- Insulinoma
- Milk Proteins
- Promoter Regions, Genetic
- Proteins
- RNA, Messenger
- Rats
- STAT5 Transcription Factor
- Trans-Activators
- Tumor Cells, Cultured
- Up-Regulation