Disease relevance of Sstr5

• The mRNA for sst1 was detected in 65% of the ovarian cancer specimens, while the incidence of sst2A, sst3 and sst5 was 65%, 41% and 24%, respectively [1].
• In a series of human corticotroph adenomas, we recently found predominant mRNA expression of somatostatin (SS) receptor subtype 5 (sst5) [2].
• All three carcinomas expressed high-affinity sst2 and sst5 receptors [3].

High impact information on Sstr5

• Somatostatin receptor type 5 modulates somatostatin receptor type 2 regulation of adrenocorticotropin secretion [4].
• SUMMARY BACKGROUND DATA: The sulfonylurea receptor (Sur) and somatostatin receptor type 5 (SSTR5) play an integral role in the regulatory pathways of the endocrine pancreas [5].
• In summary, the mouse sst5 gene promoter has been characterized, and functional activity and nuclear factor interactions were mapped to two specific promoter regions [6].
• The region between -67 and -47 appears to contain a nucleotide sequence critical for basal transcriptional regulation of the mouse sst5 gene in pituitary cells [6].
• The effects of SRIF-14 were mimicked by 100 nM L-362,855 (a partial agonist at sst5 receptors), but not BIM-23027 or NNC-26,9100 (selective agonists at sst2 and sst4 receptors, respectively) [7].

Biological context of Sstr5

• Sequence comparison between the complementary DNA and the gene revealed that the mouse sst5 gene contains 3 exons and 2 introns [8].
• Immunohistochemistry analysis showed that SSTR5 gene expression was absent in beta cells at three months of age [9].
• SSTR5 ablation in islet results in alterations in glucose homeostasis in mice [9].
• Smstr1 through Smstr5 were localized to mouse chromosomes 12, 11, 15, 2, and 17, respectively [10].
• We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding [11].

Anatomical context of Sstr5

• To investigate the consequences of gene ablation of SSTR5 in the mouse pancreas, we have generated a mouse model in which the SSTR5 gene was specifically knocked down in the pancreatic beta cells (betaSSTR5Kd) using the Cre-lox system [9].
• In this study we have used double immunostaining to show that the sst5 protein is expressed exclusively in the beta-cells of rat pancreatic islets and localizes with insulin-secreting alpha-cells [12].

Associations of Sstr5 with chemical compounds

• We have shown that sst5 transcripts and protein are induced by thyroid hormone in TtT-97 thyrotropic tumors [8].
• Cyanamid 154806, a selective sst2 receptor antagonist, but not BIM-23056, an antagonist at sst5 receptors, prevented the SRIF-14 effect [13].
• After 72 h, the multiligand SS analog SOM230, which has a very high sst5 binding affinity, but not Octreotide (OCT), significantly inhibited basal ACTH release [2].
• (3) Addition of excess nonlabeled peptides selective for sst2 (BIM23014, BIM23060, BIM23068) suppressed the formation of the complex 57 kD whereas addition of BIM23052 or BIM23056 (sst5 and sst3 selective respectively) does not [14].

Other interactions of Sstr5

• The profile of [125I]Tyr3-octreotide labelled sites in rat cortex correlates better with recombinant sst2 than sst3 or sst5 binding profiles [15].
• These results support the hypothesis that SSTR5 plays a pivotal role in the regulation of insulin secretion in the mouse pancreas [9].
• Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding [11].
• Native somatostatin sst2 and sst5 receptors functionally coupled to Gi/o-protein, but not to the serum response element in AtT-20 mouse tumour corticotrophs [16].

Analytical, diagnostic and therapeutic context of Sstr5

• Quantitative PCR analysis showed that DEX lowered sst(2A+2B) mRNA expression significantly after 24 and 48 h, whereas sst5 mRNA levels were not significantly affected by DEX treatment [2].
• Subtypes 2 and 5 of somatostatin receptor proteins (sst2 and sst5, respectively) were analyzed using immunohistochemistry and immunoblotting [3].

References