Identification of a growth hormone-responsive STAT5-binding element in the rat insulin 1 gene

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E D Galsgaard, F Gouilleux, B Groner, P Serup, N Billestrup, Jens Høiriis Nielsen

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.
OriginalsprogEngelsk
TidsskriftMolecular endocrinology (Baltimore, Md.)
Vol/bind10
Udgave nummer6
Sider (fra-til)652-60
Antal sider9
ISSN0888-8809
StatusUdgivet - jun. 1996

ID: 47972994