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 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 Use of the somatostatin analogue octreotide to localise and manage somatostatin-producing tumours

Gut ◽  
1998 ◽  
Vol 42 (6) ◽  
pp. 792-794 ◽  
Author(s):  
S Angeletti ◽  
V D Corleto ◽  
O Schillaci ◽  
M Marignani ◽  
B Annibale ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogue ◽  
Pancreatic Lesion ◽  
Endocrine Tumours ◽  
Hepatic Involvement ◽  
Receptor Scintigraphy ◽  
Octreotide Therapy ◽  
Octreotide Treatment ◽  
Few Data

Background—Somatostatin receptor scintigraphy (SRS) and octreotide therapy have both changed the management of gastroenteropancreatic endocrine tumours, but very few data are available on the use of SRS and octreotide to visualise and treat somatostatinomas.Method—The results of SRS and octreotide treatment in three somatostatinoma patients were examined.Results—SRS was able to detect extensive hepatic involvement in patient 1, one hepatic and one pancreatic lesion in patient 2, and one hepatic lesion in patient 3. Octreotide therapy (0.5 mg/day subcutaneously) was effective in decreasing plasma levels of somatostatin in all three patients. Symptoms (diabetes and diarrhoea) were greatly improved in the two patients with “somatostatinoma syndrome”.Conclusion—The study shows that somatostatinoma, like most other gastroenteropancreatic endocrine tumours, possesses functioning somatostatin receptors.

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.

Placental growth hormone as a potential regulator of maternal IGF-I during human pregnancy

1990 ◽  
Vol 258 (6) ◽  
pp. E1014-E1019 ◽  
Author(s):  
A. Caufriez ◽  
F. Frankenne ◽  
Y. Englert ◽  
J. Golstein ◽  
F. Cantraine ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Normal Pregnancy ◽  
Placental Lactogen ◽  
Blood Samples ◽  
Positive Correlation ◽  
Healthy Women ◽  
Progressive Return ◽  
Previous Hypothesis ◽  
Igf I ◽  
Placental Growth Hormone

Ninety-three healthy women were investigated during normal pregnancy, and 177 blood samples were obtained at various gestational stages. In 8 of the women, serial measurements were obtained over a period of 16-34 wk from 8 to 40 wk of gestation. In 13 women, daily blood samples were obtained from day 0 to day 6 after delivery. Insulin-like growth factor I (IGF-I) and human placental lactogen (hPL) were measured by radioimmunoassays. Growth hormone (GH) was estimated by two monoclonal antibody-based radioimmunoassays insensitive to physiological concentrations of hPL: the K24 assay, which recognizes only pituitary hGH, and the 5B4 assay, which reacts with all the known pituitary as well as placental GH variants. Placental GH was distinguished from the main pituitary variant through its specific immunoreactivity pattern. Mean plasma levels of IGF-I were relatively stable until 29-30 wk gestation, then increased progressively to reach a maximum at 35-36 wk. Regardless of gestational age, individual IGF-I values exhibited a highly significant positive correlation with placental GH, reflected by 5B4 immunoreactivity, whereas the correlation between IGF-I and hPL was not statistically significant. Considering each 2-wk gestational period separately, we found a positive correlation between IGF-I and 5B4 hGH at 31-32 wk. Conversely, no evidence of correlation was found between IGF-I and hPL at any period. After delivery, IGF-I evolution exhibited a biphasic pattern, with an initial decrease to low values followed by a progressive return toward levels found in nonpregnant healthy women. These results strengthen our previous hypothesis that placental growth hormone is involved in the control mechanism of serum IGF-I levels in normal pregnant women.

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.

Functional somatostatin receptors on a rat pancreatic acinar cell line

1988 ◽  
Vol 255 (1) ◽  
pp. G113-G120 ◽  
Author(s):  
N. Viguerie ◽  
N. Tahiri-Jouti ◽  
J. P. Esteve ◽  
P. Clerc ◽  
C. Logsdon ◽  
...  
Keyword(s):  
Cell Line ◽  
Acinar Cell ◽  
Pertussis Toxin ◽  
Binding Capacity ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Pancreatic Acinar Cell ◽  
Membrane Receptors ◽  
Dependent Manner ◽  
Camp Formation

Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I-[Tyr11]somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites (Kd = 0.55 +/- 0.06 nM) with a maximal binding capacity of 258 +/- 20 fmol/10(6) cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide (Mr 80,000) containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation (IC50 = 0.4 nM) was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. We conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase.

METABOLISM OF 17α-HYDROXYPROGESTERONE-4-14C-17α-CAPROATE BY HOMOGENATES OF RAT LIVER AND HUMAN PLACENTA

1961 ◽  
Vol 36 (4) ◽  
pp. 511-519 ◽  
Author(s):  
Margaret Wiener ◽  
Charles I. Lupa ◽  
E. Jürgen Plotz
Keyword(s):  
Rat Liver ◽  
Human Placenta ◽  
Steric Hindrance ◽  
Placental Tissue ◽  
Caproic Acid ◽  
Major Product ◽  
Side Chain ◽  
Anaerobic Conditions ◽  
Prolonged Action ◽  
Long Acting

ABSTRACT 17α-hydroxyprogesterone-4-14C-17α-caproate (HPC), a long-acting progestational agent, was incubated with homogenates of rat liver and human placenta. The rat liver was found to reduce Ring A of HPC under anaerobic conditions to form allopregnane-3β,17α-diol-20-one-17α-caproate and pregnane-3β,17α-diol-20-one-17α-caproate, the allopregnane isomer being the major product. The caproic acid ester was neither removed nor altered during the incubation. Placental tissue did not attack HPC under conditions where the 20-ketone of progesterone was reduced. It is postulated that this absence of attack on the side chain is due to steric hindrance from the caproate ester, and that this may account for the prolonged action of HPC.

scholarly journals Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 232
Author(s):  
Rashmi G. Shah ◽  
Marine A. Merlin ◽  
Samuel Adant ◽  
Fayçal Zine-Eddine ◽  
Jean-Mathieu Beauregard ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Objective Response ◽  
Peptide Receptor Radionuclide Therapy ◽  
Normal Cells ◽  
Radiation Delivery ◽  
Different Types ◽  
Pre Treatment ◽  
High Doses ◽  
Low Dose Chemotherapy

The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.

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