Hormonal regulation of the human ghrelin receptor gene transcription.

Abstract The aim of this study is to clarify the hormonal regulation of the human ghrelin receptor gene expression in GH 3 cells transfected with our previously cloned 5′-flanking region inserted into a luciferase reporter vector. Phorbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to −669 but not to −608 base pairs (bp). Glucocorticoid caused a weak but significant inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to −531 but not to −475 bp. Electrophoretic mobility shift assay resulted in binding of oligonucleotides between −669 and −640 bp, and between −520 and −491 bp to GH 3 cell nuclear proteins unlike AP 2 or glucocorticoid receptor. These results suggest that both TPA/Bay K8644 and glucocorticoid downregulate human ghrelin receptor gene expression through the transcriptional mechanism involving some nuclear factors.