Genomic structure and transcriptional regulation of the human somatostatinreceptor type 2

Somatostatin exerts inhibitory effects on virtuality all endocrine and exoc rine secretions. The somatostatin receptor subtype 2 (sst2) acts as a criti cal molecule for growth hormone regulation and cell proliferation. We inves tigated the structure and regulation of the human sst2 gene. A genomic clon e including the sst2 gene was isolated, 1.5 kb of the promoter was sequence d and putative transcription factor binding sites were identified. The tran scription start site was located 93 nucleotides upstream of the translation start site. The nucleotide sequences of the complete gene and 0.5 kb of 3' region were determined. A possible polyadenylation signal was identified. Transcriptional regulation was investigated by transient transfections usin g various promoter fragments. A - 1100 sst2 promoter directed significant l evels of luciferase expression in GH4 rat pituitary cells and Skut1-B endom etrium cells whereas only low activity was detected in JEG3 chorion carcino ma cells or COS-7 monkey kidney cells. A minimal -252 promoter allowed cell specific expression. We did not find any regulation of the sst2 promoter b y somatostatin, forskolin, TRH, TPA, T3, and 17 beta-estradiol. Glucocortic oids lead to a significant inhibition of sst2 promoter activity. Further ma pping suggest a glucocorticoid-responsive element between -905 and -707 and between -252 and -163. These studies demonstrate the nature of the human s st2 gene and identify its 5' and 3' flanking regions. Furthermore, specific activity of the promoter and regulation by various hormones is demonstrate d. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.