Hormonal regulation of the human ghrelin receptor gene transcription

The aim of this study is to clarify the hormonal regulation of the human gh relin receptor gene expression in GH(3) cells transfected with our previous ly cloned 5'-flanking region inserted into a luciferase reporter vector. Ph orbor 12-tetradecanoate 13-acetate (TPA) with simultaneous addition of Bay K8644 mimicking ghrelin action caused a significant inhibition of the lucif erase activity through the ghrelin receptor gene upstream proximal to -669 but not to -608 base pairs (bp). Glucocorticoid caused a weak but significa nt inhibition of the luciferase activity through the ghrelin receptor gene upstream proximal to -531 but not to -475 bp. Electrophoretic mobility shif t assay resulted in binding of oligonucleotides between -669 and -640 bp, a nd 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. (C) 2001 Acad emic Press.