A variation in a Pit-1 site in the growth hormone gene (GH1) promoter induces a differential transcriptional activity

The proximal promoter of the human growth hormone gene (GH1) is highly polymorphic. We tested if promoter haplotypes differing at possibly functional sites, namely −278T/G (in the NF1 binding site), −75A/G (in the proximal Pit-1 binding site) and −57G/T (in the VDR binding site), induced a different luciferase activity when transfected in a rat pituitary cell line. The presence of a G instead of an A at position −75 induced a more than two-fold reduced activity (p < 0.0001). In accordance with this findings the electrophoretic mobility shift assay demonstrated a reduced affinity of the −75G for the pituitary transcription factor Pit-1. Despite the strong effect of this polymorphism in vitro, the −75G variation was not associated to an impairment of the GH secretion in vivo.