Ask about this productRelated genes to: SSTR5 antibody
- Gene:
- SSTR5 NIH gene
- Name:
- somatostatin receptor 5
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-05-12
- Date modifiied:
- 2015-08-26
Related products to: SSTR5 antibody
Related articles to: SSTR5 antibody
- Somatostatin receptor subtype 5 (SSTR5), a G protein-coupled receptor (GPCR) highly expressed in the pituitary gland, plays a pivotal role in regulating adrenocorticotropic hormone (ACTH) secretion. While SSTR5 homodimerization has been observed in heterologous expression systems, its in situ existence, structural dynamics, and functional relevance in clinical pathology remain elusive. In this study, we provide the first evidence of endogenous SSTR5 homodimers in human corticotroph adenomas. Further analysis reveals that SSTR5 dimerization is mediated by multiple transmembrane (TM) interfaces and, uniquely among GPCRs, lacks ligand-induced conformational rearrangement. Functionally, we demonstrate that a stabilized dimeric conformation induces signaling bias by impairing both constitutive Gi protein activation and agonist-induced beta-arrestin2 recruitment. In cellular models of corticotroph adenomas, SSTR5 dimerization significantly attenuates the receptor's capacity to suppress hormone secretion and diminishes responsiveness to the clinical agonist pasireotide. Furthermore, we identified a natural genetic variant (V270I) that modulates dimerization efficiency, potentially serving as a biomarker for therapeutic sensitivity. Collectively, these findings establish SSTR5 homodimerization as a critical determinant of receptor signaling and a key modulator of pharmacological efficacy in the treatment of corticotroph adenomas. - Source: PubMed
Zhou HanyangLi ChuanbaoGu WeitingFeng YaoLi XiaoyingChen DeshengLiu YantingLiu FangCheng YijunXu ChanjuanTang HaoWu Zhe BaoXue Li - : Somatostatin receptors (SSTRs) are pivotal diagnostic and therapeutic targets in well-differentiated neuroendocrine neoplasms (NENs). SSTR-directed treatment strategies rely on sufficient SSTR2 expression. Thus, receptor loss during dedifferentiation limits therapeutic efficacy. Preclinical data suggest pharmacologic modulation of SSTRs' expression. However, there are no robust data on the effect of NEN-specific systemic treatments on SSTRs' expression and function. : We systematically evaluated the effects of six systemic agents commonly used in NEN therapy-isplatin, etoposide, 5-fluorouracil (5-FU), streptozotocin (STZ), temozolomide (TMZ), and everolimus-on SSTR2 and SSTR5 expression, as well as on uptake of Ga-DOTATOC, in BON-1 and QGP-1 cells, as well as the MS-18 cell line. Analyses included qRT-PCR, Western blotting, immunohistochemistry, and radiopeptide uptake assays. : Systemic agents modulated SSTR expression and radioligand uptake in a drug- and cell line-dependent manner. Etoposide consistently upregulated SSTR2 expression and significantly increased radioligand uptake across all three cell lines. TMZ enhanced SSTR2 expression and uptake in BON-1 cells, but reduced uptake in QGP-1 and MS-18 cells. In contrast, 5-FU, STZ, cisplatin, and everolimus showed heterogeneous, compound- and cell line-specific effects on SSTR2 expression and Ga-DOTATOC uptake, including both up- and downregulation depending on the model. : All agents under investigation affect SSTR expression in vitro, while etoposide is identified as the most consistent enhancer of SSTR2's expression and function across cellular NEN models. Our findings highlight both the potential and the risks of systemic therapy-induced receptor modulation and therefore support further investigation of treatment sequencing strategies to optimize SSTR-targeted approaches. However, further studies are required to translate these observations to a clinical setting. - Source: PubMed
Publication date: 2026/04/25
Däubler ChristofBöttcher ClaraLandwehr Laura-SophieHartrampf Philipp EMeining AlexanderWerner Rudolf AZhi YingjunKimpel OtiliaKloock SimonDischinger UlrichWeich AlexanderRogoll Dorothee - Somatostatin receptor 5 (SSTR5) negatively regulates growth hormone (GH) secretion in the human pituitary. Current therapy for GH deficiency (GHD) relies on exogenous recombinant GH injections, posing a significant treatment burden. SCO-240 is a novel, oral selective SSTR5 antagonist designed to stimulate the GH/insulin-like growth factor 1 (IGF-1) axis by "releasing the brake" on endogenous GH secretion. We evaluated whether sustained SSTR5 antagonism could induce a durable IGF-1 response while maintaining endocrine selectivity and metabolic neutrality. - Source: PubMed
Publication date: 2026/05/07
Nishizaki HarunobuSugama JunHirose HidekiKoyama RyokichiWatanabe MasanoriMoritoh Yusuke - Somatotropinomas are a subtype of pituitary adenomas that have a particular predilection to invade the cavernous sinus. The objective of this systematic review was to examine the evidence regarding the molecular basis for cavernous sinus invasion in somatotropinomas. This review was conducted in accordance with the 2020 PRISMA guidelines on 13 April 2025. Inclusion criteria were reports of associations between somatotropinoma molecular changes and cavernous sinus invasion in adult patients. Title/abstract screening and full-text screening were performed, with studies assessed for risk of bias using the Newcastle-Ottawa scale. A total of 43 studies were identified, encompassing 1,824 patients (724 invasive tumours). Overall, 33 studies identified molecules that were upregulated in invasive tumours and 20 studies identified molecules that were downregulated. Few studies incorporated modern proteomic or transcriptomic techniques. Risk of bias was low with a mean Newcastle-Ottawa scale score of 7.0 (±0.6). Molecules associated with invasion were related to epithelial-mesenchymal transition (E-cadherin, ESRP1, fascin-1, and MMP-9), cellular proliferation (PTTG, AIP, TCERG1, EIF2β, E2F1, Notch 2, STAT3, ARRB1, TGFB1, SMAD3, SOX9, SGK1, MAGEA6 DLL3, EGFL7, and pEGFR), hormonal signalling (GNAS, DRD5, DRD1, sst5TMD4, SSTR2, and SSTR5), and tumour angiogenesis (VEGF and Drp1). These molecular variations present a possible explanation for the proclivity of somatotropinomas for the cavernous sinus. Identified molecules represent options for novel targeted therapies or biomarkers that could inform prognostication. Modern proteomic and transcriptomic techniques and larger somatotropinoma datasets are required to further elucidate the molecular pathways responsible for cavernous sinus invasion in somatotropinomas. - Source: PubMed
Publication date: 2026/05/11
Ovenden Christopher DillonCandy NicholasBacchi StephenSorvina AlexandraCastle-Kirszbaum MendelPoonnoose SantoshVrodos NikitasJukes AlistairSantoreneos StephenTorpy David JPsaltis AlkisDe Sousa Sunita - TGR5 represents a compelling therapeutic target for metabolic disorders, yet the clinical development of its agonists has been constrained by gallbladder filling. Antagonism of SSTR5 enhances GLP-1 secretion and promotes gallbladder contraction signaling, supporting incretin-mediated glycemic control, and counteracting TGR5-mediated gallbladder filling. Guided by this rationale, a series of dual-target small molecules were rationally designed and synthesized to concurrently activate TGR5 and antagonize SSTR5. Among them, compound (hTGR5 EC = 5.91 nM; hSSTR5 IC = 4.37 nM) exhibited potent and balanced in vitro activity at both TGR5 and SSTR5, although the series displays suboptimal physicochemical and metabolic properties. In vivo, compound improved glucose tolerance and alleviated gallbladder filling at pharmacologically relevant doses. Collectively, these findings establish a proof of concept for dual TGR5/SSTR5 modulation as a promising therapeutic modality, providing a viable strategy to achieve potent metabolic efficacy with reduced risk of adverse effects. - Source: PubMed
Publication date: 2026/04/06
Song ChuhuaWang YuHan XiaoyuLi MengyaGuo ShimengChen LiliSun JunHan FanghuiShi YuqiHu JingZhao JialinWang KaiXie XinShen Jianhua