Transcriptional regulation of the human somatostatin receptor subtypes (sst 1–5) in adrenal cortex and medulla cells

Background: Somatostatin (SRIF) is a widely distributed peptide with inhibitory effects on cell proliferation in normal and tumor tissues. In RNA obtained from normal adrenal gland, we demonstrated significant expression of all five ssts using RT/PCR. Pheochromocytomas, Conn adenomas, Cushing's adenomas and nonfunctional adenomas showed specific sst expression profiles for each tumor typ. To understand the regulation of sst expression in the adrenal gland, we investigated the transcriptional activity of the sst 1–5 promoters.

Material and Methods: Transcription start sites for the various sst genes were previously identified. Promoter regions (-2725sst1, -1100sst2, -2536sst3, -984sst4, and -1740sst5) obtained by PCR on human genomic DNA were cloned upstream of the luciferase gene into a luciferase expression vector. After transient transfection, the promoter activity was determined using a luciferase reporter gene assay. We investigated the promoter activity in mouse adrenocortical Y1 cells and rat adrenal medulla PC12 cells. GH4 rat pituitary cells and Cos-7 monkey kidney cells were used as positive and negative controls, respectively.

Results: GH4 demonstrated significant transcriptional promoter activity of all five ssts, whereas no significant promoter activity was found in Cos-7 cells. In Y1 cells, we demonstrated significant transcriptional activity of the sst 1–5 promoters. In contrast, the tested promoter regions showed no activity in the PC12 cells. Elements transducing the transcriptional activity in Y1 cells were localized to -368 to -233, -325 to -252, -2536 to -1896, -266 to -209, -101 to -1, for sst1, sst2, sst3, sst4, and sst5, respectively.

Conclusions: Sst promoter regions identified in the pituitary may also regulate sst 1–5 expression in the adrenal cortex. In contrast, alternative promoter regions may regulate sst transcription in the adrenal medulla.