scholarly journals Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

2008 ◽  
Vol 52 (8) ◽  
pp. 1288-1295 ◽  
Author(s):  
Leonardo Vieira Neto ◽  
Giselle Fernandes Taboada ◽  
Mônica Roberto Gadelha
Keyword(s):  
Growth Hormone ◽  
Quantitative Analysis ◽  
Dopamine Receptor ◽  
Molecular Analysis ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Laboratory Data ◽  
Octreotide Lar ◽  
Acute Test ◽  
Igf I

We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

scholarly journals Octreotide long-acting repeatable and lanreotide Autogel are equally effective in controlling growth hormone secretion in acromegalic patients

2004 ◽  
pp. 489-495 ◽  
Author(s):  
SW van Thiel ◽  
JA Romijn ◽  
NR Biermasz ◽  
BE Ballieux ◽  
M Frolich ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Binding Affinity ◽  
Receptor Subtype ◽  
Somatostatin Analogue ◽  
Deconvolution Analysis ◽  
Octreotide Lar ◽  
Gh Secretion ◽  
Igf I ◽  
Long Acting ◽  
Lanreotide Autogel

OBJECTIVE: Recently a new depot preparation of the long-acting somatostatin analogue, lanreotide Autogel was introduced for the treatment of acromegaly. Like octreotide long-acting repeatable (LAR), it has high binding affinity for the somatostatin receptor subtype SSTR 2 and less binding affinity for SSTR 5. We hypothesized that the ability to suppress growth hormone (GH) secretion in patients with acromegaly would be similar for these depot preparations. PATIENTS AND STUDY DESIGN: Seven patients (mean age+/-S.E.M. 48.4+/-7 years) on long-term octreotide LAR treatment at a monthly injection interval for a mean of 2.8 years were enrolled in the study. They underwent a GH secretory profile study with 10 min sampling for 24 h, 28 days after an injection. At 2, 4 and 6 weeks after the next injection fasting GH profiles (every 30 min for 3.5 h) and serum IGF-I measurements were measured. These investigations were repeated 12 months later, when the patients were on an individually titrated stable dose of lanreotide Autogel. RESULTS: Secretory characteristics and total 24 h GH secretion, estimated by deconvolution analysis of the 10 min 24 h plasma GH concentrations, did not show differences between these two long-acting somatostatin analogues. Both drugs were equally effective in GH and IGF-I suppression as measured at 2, 4 and also at 6 weeks following an injection. CONCLUSION: The efficacy of lanreotide Autogel and octreotide LAR was equal, notwithstanding that these drugs are administered in a different way and have different pharmacokinetics.

The Somatostatin Analog Octreotide Inhibits Growth of Interleukin-6 (IL-6)–Dependent and IL-6–Independent Human Multiple Myeloma Cell Lines

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1724-1731 ◽  
Author(s):  
Patrik Georgii-Hemming ◽  
Thomas Strömberg ◽  
Eva Tiensuu Janson ◽  
Mats Stridsberg ◽  
Helena Jernberg Wiklund ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Plasma Cells ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analog ◽  
Igf I ◽  
Human Multiple Myeloma

Abstract Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)–dependent and the IL-6–independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4+ plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.

scholarly journals Expression of Somatostatin Receptor SST4 in Human Placenta and Absence of Octreotide Effect on Human Placental Growth Hormone Concentration during Pregnancy1

1997 ◽  
Vol 82 (11) ◽  
pp. 3771-3776 ◽  
Author(s):  
Philippe Caron ◽  
Louis Buscail ◽  
Albert Beckers ◽  
Jean-Pierre Estève ◽  
Ahmed Igout ◽  
...  
Keyword(s):  
Human Placenta ◽  
Binding Capacity ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Placental Tissue ◽  
Normal Pregnancy ◽  
Ribonucleic Acids ◽  
Igf I ◽  
Placental Growth Hormone ◽  
Octreotide Treatment

In pregnancy, the human placenta GH acts as a growth-promoting hormone and appears to be the main stimulator of insulin-like growth factor I (IGF-I) secretion. In a woman with a TSH-secreting macroadenoma, successful treatment with the somatostatin analog octreotide was conducted during the first month and the second half of pregnancy without side-effects on placental and fetal development. As observed in normal pregnancy, both serum placental GH and IGF-I levels increased throughout pregnancy and dropped sharply after delivery. In placental membranes from both treated and healthy untreated patients, we demonstrated the presence of high affinity binding sites for somatostatin-14 (Kd, 4.6 and 5.3 nmol/L; binding capacity, 1.53 and 1.35 pmol/mg protein, respectively). These receptors displayed low affinity for octreotide (IC50, 1.2–2 μmol/L), suggesting the presence of SST1 and/or SST4 receptors. We found that messenger ribonucleic acids of these two subtypes were expressed in both human placental tissue and purified human cytotrophoblast cells. Finally, the SST1-selective analog, des-AA1,2,5[d-Trp8,IAmp9]S-14 had low affinity for placental somatostatin receptors. These results argue in favor of the presence of the SST4 subtype in human placenta. At the doses administered, octreotide did not bind to placental somatostatin receptors. Our results may explain the absence of changes in both human placental GH and IGF-I concentrations that we observed during octreotide treatment.

scholarly journals Analysis of Somatostatin Receptors 2 and 5 Polymorphisms in Patients with Acromegaly

2005 ◽  
Vol 90 (8) ◽  
pp. 4824-4828 ◽  
Author(s):  
M. Filopanti ◽  
C. Ronchi ◽  
E. Ballarè ◽  
S. Bondioni ◽  
A. G. Lania ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Minor Role ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Igf I ◽  
A Minor ◽  
Serum Gh

Objective: The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients. Study Design: Three single nucleotide polymorphisms (a-83 g, c-57 g, and t80c) of SSTR2 and three (t-461c, c325t, and c1004t) of SSTR5 were analyzed in 66 acromegalic patients with different responsiveness to somatostatin analogs and 66 healthy controls. Results: Allele frequencies in patients and controls were similar. No association between SSTR2 genotypes and GH and IGF-I levels was found. When considering SSTR5 variants, patients homozygous or heterozygous for the substitution c1004 (P+) showed basal IGF-I levels significantly lower than patients homozygous for 1004t (P−). Moreover, serum GH levels were lower in patients with P+/T− haplotype (having c1004 allele and no t-461 allele) than in those with P−/T+. No correlation between SSTR2 and SSTR5 genotypes, responsiveness to somatostatin therapy, and mRNA expression in the removed adenomas (n = 10) was found. Conclusions: These data suggest a role for SSTR5 t–461c and c1004t alleles in influencing GH and IGF-I levels in patients with acromegaly, whereas SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs.

The Somatostatin Analog Octreotide Inhibits Growth of Interleukin-6 (IL-6)–Dependent and IL-6–Independent Human Multiple Myeloma Cell Lines

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1724-1731
Author(s):  
Patrik Georgii-Hemming ◽  
Thomas Strömberg ◽  
Eva Tiensuu Janson ◽  
Mats Stridsberg ◽  
Helena Jernberg Wiklund ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Plasma Cells ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analog ◽  
Igf I ◽  
Human Multiple Myeloma

Somatostatin and its analogs can inhibit growth in several cell types, in part by interfering with insulin-like growth factor-I (IGF-I) signaling. Our previous studies point to the importance of paracrine and autocrine IGF-I in the support of growth and survival of human multiple myeloma (MM) cell lines. In this report, we have investigated the potential role of a somatostatin analog, octreotide, in regulating growth and/or survival in MM. The results show that all MM cell lines express functional somatostatin receptors (sst). The MM cell lines express the subtypes sst2, sst3, and predominantly sst5 as determined by reverse-transcriptase polymerase chain reaction and fluorescence-activated cell sorter analysis. Octreotide inhibited the growth of both the interleukin-6 (IL-6)–dependent and the IL-6–independent MM cell lines. The effect is mainly cytostatic, resulting in 25% to 45% growth inhibition, and in three of eight of the MM cell lines a weak induction of apoptosis was recorded. Our results also show that octreotide may act as an inducer of apoptosis in primary B-B4+ plasma cells isolated from bone marrow of MM patients. In conclusion, the results show a novel pathway for growth inhibition of MM cells: the activation of somatostatin receptor signaling.

Insulin and growth hormone stimulate somatostatin receptor (SSTR) expression by inducing transcription of SSTR mRNAs and by upregulating cell surface SSTRs

2006 ◽  
Vol 291 (1) ◽  
pp. R163-R169 ◽  
Author(s):  
Laura E. Nelson ◽  
Mark A. Sheridan
Keyword(s):  
Growth Hormone ◽  
Rainbow Trout ◽  
Cell Surface ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Chinese Hamster ◽  
Functional Expression ◽  
Surface Expression ◽  
Dependent Manner ◽  
The Stability

This study examined the effects of insulin (INS) and growth hormone (GH) on mRNA and functional expression of somatostatin receptors (SSTRs). Rainbow trout liver was used as a model system to evaluate the direct effects of INS and GH on mRNA expression of three SSTR subtypes characterized previously from this species: SSTR1A, SSTR1B, and SSTR2. INS and GH directly stimulated steady-state levels of all SSTR mRNAs in a concentration- and time-dependent manner; however, the pattern of expression was hormone and SSTR subtype specific. INS stimulated SSTR2 expression to a greater extent than SSTR1A or SSTR1B expression, whereas GH stimulated SSTR2 and SSTR1B expression to a similar extent, with SSTR2 and SSTR1B expression being more responsive to GH than SSTR1A. Whether INS- or GH-stimulated SSTR expression resulted from altered rates of transcription and/or changes in mRNA stability also was investigated. Formation of nascent SSTR transcripts in nuclei isolated from rainbow trout hepatocytes was significantly stimulated by INS and GH. Neither INS nor GH, however, affected the stability of SSTR mRNAs. Functional expression of SSTRs was studied in Chinese hamster ovary (CHO-K1) cells stably transfected with SSTR1A or SSTR1B. Surface expression of functional SSTRs was stimulated by INS and GH. These findings indicate that INS and GH stimulate SSTR expression by regulating transcription of SSTR mRNAs and by increasing functional SSTRs on the cell surface, and they suggest that regulation of SSTRs may be important for the coordination of growth, development, and metabolism of vertebrates.

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

2007 ◽  
Vol 156 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Giselle F Taboada ◽  
Raul M Luque ◽  
Wildebranham Bastos ◽  
Renata F C Guimarães ◽  
Jorge B Marcondes ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Response To Therapy ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Octreotide Lar ◽  
Variable Expression ◽  
Igf I ◽  
Percent Decrease ◽  
Non Functioning Pituitary Adenomas

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 SSTR2>SSTR3≫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) (r=0.51 and r=0.66; P=0.05 and P=0.008). 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.

Laron syndrome – A case Report

JMS SKIMS ◽  
2017 ◽  
Vol 20 (2) ◽  
pp. 104-106
Author(s):  
Javaid Ahmad Bhat ◽  
Moomin Hussain Bhat ◽  
Hilal Bhat ◽  
Mona Sood ◽  
Shariq Rashid Masoodi
Keyword(s):  
Growth Hormone ◽  
Case Report ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Genetic Disorder ◽  
Female Child ◽  
Receptor Signaling ◽  
Laron Syndrome ◽  
Rare Genetic Disorder ◽  
Igf I

Background : Laron & colleagues (1966) reported a rare genetic disorder in Israliei Jewish sublings which was characterized by insensitivity to growth hormone due to abnormality in growth hormone receptor or post receptor signaling pathway.Case Report: We hereby report a case of a 5 year old female child who presented to us with features similar to Laron syndrome. The diagnosis was made & confirmed by various Lab. investigations like low IGF-I levels and managed accordingly. JMS 2017; 20 (2):104-106  

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