Characterization of the intracellular mechanisms mediating somatostatin and lanreotide inhibition of DNA synthesis and growth hormone release from dispersed human GH‐secreting pituitary adenoma cells <i>in vitro</i>

Florio, Tullio; Thellung, Stefano; Corsaro, Alessandro; Bocca, Liliana; Arena, Sara; Pattarozzi, Alessandra; Villa, Valentina; Massa, Alessandro; Diana, Fabrizio; Schettini, Daria; Barbieri, Federica; Ravetti, Jean Louis; Spaziante, Renato; Giusti, Massimo; Schettini, Gennaro

doi:10.1046/j.1365-2265.2003.01811.x

Cited by 52 publications

(34 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this, several authors have described that patients bearing tumors with the highest SSTR2 expression respond better to SA treatment in terms of hormonal control (19)(20)(21)23). Some groups have also studied the in vitro anti-proliferative action of SA and its correlation with the tumor SSTR expression pattern (26)(27)(28). Somatostatin, lanreotide, SSTR1, SSTR2, and SSTR5 ligands (BIM-23926, BIM-23190, and BIM-23268) have been shown to effectively reduce cell viability (26,27).…”

Section: Introductionmentioning

confidence: 66%

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Taboada

Luque

Neto

et al. 2008

European Journal of Endocrinology

163

110

View full text Add to dashboard Cite

Objective: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. Design and methods: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). Results: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098, 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (rZ0.49, P!0.027 and rZ0.49, P!0.029 respectively) and 6 (rZ0.59, P!0.006 and rZ0.58, P!0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (rZK0.52, PZ0.016, nZ21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), PZ0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% -area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (rZ0.79, PZ0.002, nZ12). Conclusions: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR. European Journal of Endocrinology 158 295-303

show abstract

Section: Introductionmentioning

confidence: 66%

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Taboada

Luque

Neto

et al. 2008

European Journal of Endocrinology

163

110

View full text Add to dashboard Cite

show abstract

“…SRIF is associated with increased protein phosphatase activity in both human GH-secreting pituitary adenoma cells and rat cell lines as well as human non-functioning pituitary tumors (Cervia & Bagnoli 2007). SRIF increases tyrosine phosphatase activity and was associated with the inhibition of cell growth in human GH-secreting pituitary tumor cells in vitro (Florio et al 2003), while serine/threonine phosphatase activity participates in SRIF-mediated regulation of Ca 2C influx through dephosphorylation of Ca 2C and K C voltage-activated (BK) channels (White et al 1991).…”

Section: Protein Phosphatase Pathwaysmentioning

confidence: 99%

Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

Eigler¹,

Ben-Shlomo²

2014

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The somatostatin (SRIF) system, which includes the SRIF ligand and receptors, regulates anterior pituitary gland function, mainly inhibiting hormone secretion and to some extent pituitary tumor cell growth. SRIF-14 via its cognate G-protein-coupled receptors (subtypes 1-5) activates multiple cellular signaling pathways including adenylate cyclase/cAMP, MAPK, ion channel-dependent pathways, and others. In addition, recent data have suggested SRIF-independent constitutive SRIF receptor activity responsible for GH and ACTH inhibition in vitro. This review summarizes current knowledge on ligand-dependent and independent SRIF receptor molecular and functional effects on hormone-secreting cells in the anterior pituitary gland.

show abstract

“…All the five genes are expressed in normal adult human pituitaries, however, SSTR4 mRNA is found at extremely low levels (15,16). Somatostatin receptors expression in pituitary adenomas is reported to be highly variable within and between tumor subtypes (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In studies conducted with non-pituitary tissues, all SSTR subtypes have been shown to have anti-proliferative effects in some cell types and SSTR2 and SSTR3 were specifically shown to initiate apoptosis (34).…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of somatostatin receptor subtype (SSTR1–5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas

et al. 2007

View full text Add to dashboard Cite

Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2OSSTR3[SSTR1\SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (rZ0.51 and rZ0.66; PZ0.05 and PZ0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide. 156 65-74 European Journal of Endocrinology

show abstract

Characterization of the intracellular mechanisms mediating somatostatin and lanreotide inhibition of DNA synthesis and growth hormone release from dispersed human GH‐secreting pituitary adenoma cells in vitro

Cited by 52 publications

References 57 publications

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Quantitative analysis of somatostatin receptor subtypes (1–5) gene expression levels in somatotropinomas and correlation to in vivo hormonal and tumor volume responses to treatment with octreotide LAR

Somatostatin system: molecular mechanisms regulating anterior pituitary hormones

Quantitative analysis of somatostatin receptor subtype (SSTR1–5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas

Contact Info

Product

Resources

About