Gene structure and regulation of the somatostatin receptor type 2

The diverse biological effects of the hormone somatostatin are mediated by five genetic different receptor subtypes (sst1-sst5), which belong to the superfamily of G-protein coupled receptors with seven transmembrane domains. The sst2 subtype is unique among the somatostatin receptors in its structure, since it is expressed in two protein variants which differ within their carboxy-terminal ends, generated by alternative splicing. Within the 5' untranslated region of the gene two introns separate three transcriptional units with distinct promoters. Due to the latter feature, the sst2 gene is also unique among all somatostatin receptor genes regarding its transcriptional regulation. The three alternative promoters are tissue specifically active and show alternative responsiveness to extracellular signals. The second sst2 promoter is important for expression of the gene in tissues where somatostatin has essential physiological functions, such as brain, pituitary and gastrointestinal tissues. Furthermore, it contains cis-acting regulatory elements involved in the transcriptional response to elevated cyclic AMP levels and glucocorticoids.