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18 "Somatostatin"
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Special Article
Hypothalamus and Pituitary gland
Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong Jun Lim, Dong Yeob Shin, Se Hwa Kim, Min Jeong Kwon, Ha Young Kim, Jin Hwa Kim, Dong Sun Kim, Chong Hwa Kim
Endocrinol Metab. 2019;34(1):53-62.   Published online March 21, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.1.53
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  • 11 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Citations

Citations to this article as recorded by  
  • Hydrogel-fiber-mesh-based 3D cell cultures: A new method for studying pituitary tumors
    Wooju Jeong, Sungrok Wang, Yumin Kim, Soohyun Lee, Minhu Huang, Jaeil Park, Myung-Han Yoon, Chang-Myung Oh, Cheol Ryong Ku
    Smart Materials in Medicine.2024; 5(2): 281.     CrossRef
  • Differential gene expression and pathway analysis in growth hormone-secreting pituitary tumors according to granulation pattern
    Kyungwon Kim, Yeongmin Kim, Se Hoon Kim, Ju Hyung Moon, Eui Hyun Kim, Eun Jig Lee, Chang-Myung Oh, Cheol Ryong Ku
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias
    Argyrios Periferakis, Georgios Tsigas, Aristodemos-Theodoros Periferakis, Carla Mihaela Tone, Daria Alexandra Hemes, Konstantinos Periferakis, Lamprini Troumpata, Ioana Anca Badarau, Cristian Scheau, Ana Caruntu, Ilinca Savulescu-Fiedler, Constantin Carun
    Current Issues in Molecular Biology.2024; 46(9): 9721.     CrossRef
  • Insulin-Like Growth Factor 1 as a Pillar in Acromegaly: From Diagnosis to Long-Term Management
    Mi Kyung Kim
    Endocrinology and Metabolism.2024; 39(5): 693.     CrossRef
  • Diagnosis and Management of Acromegaly: A Consensus Statement of the Pituitary Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism
    Luís Miguel Cardoso, Pedro Marques, Maria Teresa Pereira, Ana Agapito, Rui Almeida, Sara Amaral, Maria João Bugalho, Maria Begoña Cattoni, Luísa Cortez, Diana Borges Duarte, João Sequeira Duarte, Fernando Fonseca, Leonor Gomes, Inês Manique, Olinda
    Endocrinology Insights.2024; : 1.     CrossRef
  • Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association
    A Ram Hong, Ho-Cheol Kang
    Endocrinology and Metabolism.2023; 38(2): 175.     CrossRef
  • Growth Hormone Excess: Implications and Management
    Suneela Dhaneshwar, Shrishti Shandily, Vatsalya Tiwari
    Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(6): 748.     CrossRef
  • Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly
    Montserrat Marques-Pamies, Joan Gil, Elena Valassi, Marta Hernández, Betina Biagetti, Olga Giménez-Palop, Silvia Martínez, Cristina Carrato, Laura Pons, Rocío Villar-Taibo, Marta Araujo-Castro, Concepción Blanco, Inmaculada Simón, Andreu Simó-Servat, Gemm
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Evaluation and Management of Bone Health in Patients with Thyroid Diseases: a Position Statement from the Korean Thyroid Association
    A Ram Hong, Hwa Young Ahn, Bu Kyung Kim, Seong Hee Ahn, So Young Park, Min-Hee Kim, Jeongmin Lee, Sun Wook Cho, Ho-Cheol Kang
    International Journal of Thyroidology.2022; 15(1): 1.     CrossRef
  • Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy
    I. A. Ilovayskaya
    Meditsinskiy sovet = Medical Council.2022; (10): 148.     CrossRef
  • Approach of Acromegaly during Pregnancy
    Alexandru Dan Popescu, Mara Carsote, Ana Valea, Andreea Gabriela Nicola, Ionela Teodora Dascălu, Tiberiu Tircă, Jaqueline Abdul-Razzak, Mihaela Jana Țuculină
    Diagnostics.2022; 12(11): 2669.     CrossRef
  • Left to themselves: Time to target chronic pain in childhood rare diseases
    Christine B. Sieberg, Alyssa Lebel, Erin Silliman, Scott Holmes, David Borsook, Igor Elman
    Neuroscience & Biobehavioral Reviews.2021; 126: 276.     CrossRef
  • Severe respiratory failure in a patient with COVID-19 and acromegaly: rapid improvement after adding octreotide
    Jacob Luty, LesleAnn Hayward, Melanie Jackson, P Barton Duell
    BMJ Case Reports.2021; 14(8): e243900.     CrossRef
  • Precision Therapy in Acromegaly Caused by Pituitary Tumors: How Close Is It to Reality?
    Cheol Ryong Ku, Vladimir Melnikov, Zhaoyun Zhang, Eun Jig Lee
    Endocrinology and Metabolism.2020; 35(2): 206.     CrossRef
  • Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
    Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong
    The Korean Journal of Medicine.2019; 94(6): 485.     CrossRef
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Original Articles
Somatostatin Inhibits Gonadotropin Releasing Hormone Neuronal Activities in Juvenile Mice.
Seon Ah Park, Janardhan P Bhattarai, Seong Kyu Han
Endocrinol Metab. 2011;26(3):210-217.   Published online September 1, 2011
DOI: https://doi.org/10.3803/EnM.2011.26.3.210
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AbstractAbstract PDF
BACKGROUND
The gonadotropin releasing hormone (GnRH) neurons perform a pivotal function in the central regulation of fertility. Somatostatin (SST) is an important neuromodulatory peptide in the central nervous system and alters neuronal activities via G protein- coupled SST receptors. A number of studies have shown that SST modulates the reproductive axis at the hypothalamic level. However, the precise action mechanisms of SST and related receptor subtypes have yet to be fully understood. In this study, we evaluated the direct effects of SST on GnRH neurons in juvenile mice. METHODS: Juvenile (postnatal days, < PND 30) GnRH-GFP transgenic mice expressing green fluorescent protein were used in this study. Acute coronal brain slices containing the preoptic area were prepared and all identified GnRH neurons were recorded using the gramicidin perforated-patch clamp technique; type II SST receptor (SSTR2) mRNA expression was evaluated via single cell reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SST caused membrane hyperpolarization, depolarization, no response, or membrane hyperpolarization with a reduction of action potential. Most (57.7%, 30/52) of the GnRH neurons tested were hyperpolarized by SST and this SST-induced hyperpolarization was found to be concentration-dependent. The percentage of responses, membrane potential changes (MPC), and resting membrane potential (RMP) by SST were not significantly different in juvenile male and female GnRH neurons. The SST-induced hyperpolarization was maintained in the presence of tetrodotoxin (TTX), a sodium channel blocker, and an amino acid blocking cocktail (AABC) containing AP-5 (NMDA receptor antagonist), CNQX (non-NMDA glutamate receptor antagonist), picrotoxin (GABAA receptor antagonist), and strychnine (glycine receptor antagonist). SSTR2 mRNA was expressed on 10 (38%) among 26 GnRH neurons. Seglitide, an SSTR2 agonist, mimicked this SST-induced hyperpolarization (11/23 47.8%) and this response was maintained in the presence of TTX and AABC. CONCLUSION: Our data show that SST can exert potent inhibitory action against GnRH neuronal excitability via SSTR2 activation in juvenile mice.
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Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients.
Seul young Kim, Dohee Kim
J Korean Endocr Soc. 2010;25(1):37-45.   Published online March 1, 2010
DOI: https://doi.org/10.3803/jkes.2010.25.1.37
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  • 27 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Somatostatin analogues have been used as the first-line medical therapy for active acromegaly that is not completely cured, or which recurs after surgery. The aim of this study was to compare the effects of octreotide long-acting repeatable (LAR) and lanreotide Autogel. Such a comparison has not been reported in Korea. METHODS: Twenty-seven patients who had previously undergone surgery for acromegaly from December 2003 to March 2005 were included. We retrospectively investigated eight patients who underwent operation only and 19 patients who additionally received medical treatment after surgery (octreotide LAR, n = 5; lanreotide Autogel, n = 5). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels were measured. RESULTS: The mean pre-operative and post-operative levels of GH were lower in patients who underwent surgery only than in those who received adjuvant therapy, but IGF-I levels were not significantly different. In the 19 patients receiving medical treatment after unsuccessful surgery, the mean baseline GH levels were 24.2 microgram/L for octreotide LAR and 22.8 microgram/L for lanreotide Autogel (P = 0.711), and the mean GH levels 36 months post-treatment were 4.1 microgram/L and 2.5 microgram/L, respectively (P = 0.794). GH < 2.5 microgram/L represented 30% of octreotide LAR patients and 33.3% of lanreotide Autogel patients (P = 0.91). Patients with normal IGF-I levels represented 54.5% and 66.7%, respectively (P = 0.71). CONCLUSION: No significant difference in therapeutic effect of octreotide LAR and lanreotide Autogel was evident in 19 Korean acromegalic patients who were not completely cured by surgery and radiation therapy.

Citations

Citations to this article as recorded by  
  • Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement
    Sang Ouk Chin, Cheol Ryong Ku, Byung Joon Kim, Sung-Woon Kim, Kyeong Hye Park, Kee Ho Song, Seungjoon Oh, Hyun Koo Yoon, Eun Jig Lee, Jung Min Lee, Jung Soo Lim, Jung Hee Kim, Kwang Joon Kim, Heung Yong Jin, Dae Jung Kim, Kyung Ae Lee, Seong-Su Moon, Dong
    Endocrinology and Metabolism.2019; 34(1): 53.     CrossRef
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Search for Materials that Influence Human Medullary Thyroid Carcinoma Cell Proliferation.
Hyun Won Shin, Hye Won Jang, Keun Sook Kim, Ji In Lee, Ji Young Park, Sun Wook Kim, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Jae Hoon Chung
J Korean Endocr Soc. 2009;24(2):93-99.   Published online June 1, 2009
DOI: https://doi.org/10.3803/jkes.2009.24.2.93
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Surgical excision is the only effective treatment of medullary thyroid carcinoma (MTC) and there is no certain treatment for recurrence or distant metastasis. Materials that influence MTC cell proliferation were recently reported. Presently, we evaluated the influence of dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin and gastrin on MTC cell proliferation and calcitonin secretion. METHODS: Genomic DNA was extracted and sequenced from untreated thyroid TT cells and cells treated with 10-5~10-10 M dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin or gastrin, and cultured for 1~6 days. Cell proliferation was assessed using a BrdU assay at days 1, 2, 3, and 6. Calcitonin in the culture medium from dexamethasone-treated TT cells was measured at days 1~3. RESULTS: Replacement of cysteine with tryptophan at codon 634 of exon 11 was evident in treated TT cells. There was no significant difference in cell proliferation at days 1~3 in cells treated with somatostatin, progesterone, estradiol-17-beta, gastrin and forskolin, while proliferation was inhibited in dexamethasone-treated cells in a concentration-dependent manner from 10-5~10-8 M with no inhibition evident at 10-10 M. Calcitonin levels in 10-5~10-8 M dexamethasone-treated cells were decreased. CONCLUSION: Dexamethasone is a potentially useful compound to suppress MTC cell proliferation. Further studies are necessary to explore this potential further prior to clinical use.

Citations

Citations to this article as recorded by  
  • Identification of Growth Regulatory Factors in Medullary Thyroid Carcinoma Cell Line
    Young Suk Jo, Minho Shong
    Journal of Korean Endocrine Society.2009; 24(2): 84.     CrossRef
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Role of Protein kinase C in Desensitization of Somatostatin-induced Calcium Signalling in NG108-15 Cells.
Kyoung Mi Kim, Jong Ho Sung, Myung Jun Kim, Duck Joo Rhie, Yang Hyeok Jo, Sang June Hahn, Myung Suk Kim, Shin Hee Yoon, Bu Seung Kim
J Korean Endocr Soc. 2005;20(4):353-361.   Published online August 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.4.353
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AbstractAbstract PDF
BACKGROUND
Activation of G-protein coupled-somatostatin receptors induces the release of calcium from inositol 1, 4, 5-trisphosphate-sensitive intracelluar stores. G-protein-coupled receptor signaling decreases with prolonged exposure to an agonist. SEBJECTS and METHODS: Fura-2-based digital Ca2+ imaging was used to study the effects of prolonged exposure to an agonist on the somatostatin-induced intracellular Ca2+ concentration([Ca2+]i) increases in NG108-15 cells, which were differentiated with CO2-independent medium and 10micrometer forskolin. RESULTS: Exposure to somatostatin(1micrometer) for 30 min completely desensitized the NG108-15 cells to a second somatostatin-induced response. The cells recovered gradually over 20 min following washout of the somatostatin. The desensitization was not due to depletion of the intracellular Ca2+ stores, and pretreatment for 30 min with bradykinin(100nM), which activates phospholipase C, or DADLE(D-Ala2-D-Leu5 enkephalin, 1microM), which activates phospholipase C, failed to cross-desensitize the somatostatin-evoked [Ca2+]i increases. Treatment with 8-cpt-cAMP(0.1mM) for 30min did not influence the somatostatin-induced[Ca2+]i increases. Phorbol 12, 13-dibutyrate(PdBu, 1microM) blocked the response completely. Down-regulation of PKC due to 24 h exposure of PdBu (1microM) inhibited the somatostatin-induced desensitization. CONCLUSION: Prolonged exposure of somatostatin to NG108-15 cells desensitized the somatostatin-induced release of Ca2+ from the intracelluar store, with protein kinase C also involved in the desensitization.
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Efficacy of Octreotide LAR in Acromegalic Patients.
Ji Youn Kim, Jae Hwan Jee, Chan Ho Yoon, Yun Jae Chung, Byung Wan Lee, Gun Yong Cho, Sang Young Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
J Korean Endocr Soc. 2005;20(4):344-352.   Published online August 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.4.344
  • 2,459 View
  • 22 Download
  • 4 Crossref
AbstractAbstract PDF
BACKGROUND
Octreotide(OC)-LAR is a long-acting preparation of octreotide which has been effectively used to suppress GH/IGF-1 hypersecretion in acromegalic patients. The clinical response, biochemical outcomes, and safety of OC-LAR were evaluated in 27 active acromegalic patients. METHOD: 27patients with an active disease status (according to the clinical picture, GH >5microgram/L and elevated age-matched IGF-1), and previously treated with bromocriptine after surgery, comprised the study population. OC-LAR was given(20mg, i.m., every 4 week for 3 injections, then the doses were titrated individually) and the acromegalic symptoms and adverse reactions recorded. The serum levels of GH and IGF-1 were evaluated every 12 week. The acromegalic symptoms including headache, fatigue and arthralgia, improved in all patients. RESULTS: Gastrointestinal side effects were transient and mild. The levels of GH significantly decreased, from 8.9+/-3.5 to 2.9+/-2.2 microgram/L at 12 weeks(P<0.001, vs. baseline), to 2.9+/-2.1microgram/L after 24 weeks(P<0.001) and to 2.5 +/-1.3microgram/L at 48 weeks(P<0.001). The levels of IGF-1 significantly decreased, from 753.7+/-213.6 to 429.7+/-253.4 microgram/L at 12 weeks(P<0.001, vs. at baseline), to 405.7+/-213.3microgram/L at 24 weeks(P <0.001) and to 348.9+/-144.7microgram/L at 48 weeks(P<0.001). The safelevel of GH is less than 2.5microgram/L and normal age-matched IGF-1 levels were achieved in 63 and 52% of the patients, respectively. CONCLUSION: Octreotide-LAR was well tolerated and effective as an adjuvant treatment in lowering the levels of GH and IGF-1 in active acromegalic patients.

Citations

Citations to this article as recorded by  
  • Letter: Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients (J Korean Endocr Soc 25:37-45, 2010)
    Yu-Bae Ahn
    Endocrinology and Metabolism.2010; 25(2): 157.     CrossRef
  • The Effect of Octreotide LAR on GH and TSH Co-Secreting Pituitary Adenoma
    Nam Keong Kim, Yu Jin Hah, Ho Young Lee, Sang Jin Kim, Mi Kyung Kim, Keun Gyu Park, Ealmaan Kim, Hyukwon Chang, Hye Soon Kim
    Endocrinology and Metabolism.2010; 25(4): 378.     CrossRef
  • Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients
    Seul young Kim, Dohee Kim
    Journal of Korean Endocrine Society.2010; 25(1): 37.     CrossRef
  • Response: Comparison of the Efficacy of Octreotide Long-acting Repeatable and Lanreotide Autogel in Acromegalic Patients (J Korean Endocr Soc 25:37-45, 2010)
    Seul Young Kim, Dohee Kim
    Endocrinology and Metabolism.2010; 25(2): 159.     CrossRef
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Changes in Somatostatin Receptor mRNA Levels by G Protein Mutation in GH3 Cells Which Show Responsiveness to Growth Hormone-Releasing Hormone.
Eun Hee Kim, Sook Jin Sohn, Min A Lee, Sang Hee Seo, Sung Hee Ju, Dahm Lee, Hyun Ju Chung, Jee Chang Jung, Seung Joon Park
J Korean Endocr Soc. 2005;20(4):323-333.   Published online August 1, 2005
DOI: https://doi.org/10.3803/jkes.2005.20.4.323
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AbstractAbstract PDF
BACKGROUND
S: GH3 cells lack growth hormone(GH)-releasing hormone(GHRH) receptors. In this study, GH3 cells permanently transfected with human GHRH receptor cDNA(GH3-GHRHR cells), were established in order to examine the effects of GHRH and G protein mutation(gsp oncogene) on the levels of somatostatin receptor mRNA. METHODS: GH3 cells were permanently transfected with a plasmid expressing human GHRH receptor cDNA. The GHRH receptor mRNA was detected by RT-PCR. The responsiveness to GHRH was evaluated using a GHRH binding assay, Western blot analysis, Northern blot analysis, and measurements of the intracellular cAMP levels and GH release. Cells were transiently transfected with the gsp oncogene, and then treated with GHRH or octreotide for 4h. The sst1 and sst2 mRNA levels were measured using real-time RT-PCR analyses. RESULTS: GHRH receptor mRNA was detected in the GH3 cells permanently transfected with human GHRH receptor cDNA. The GHRH binding assay showed that GHRH was bound to the GH3-GHRHR cells. The GHRH treatment increased the intracellular cAMP levels, GH release, GH mRNA levels, and MAPK activity, as well as the levels of sst1 and sst2 mRNA. Transient expression of the gsp oncogene for 48h increased the cAMP, GH release, and levels of sst1 and sst2 mRNA. In the gsp-transfected GH3-GHRHR cells, GHRH stimulation resulted in decreases in the magnitude of the increase in the levels of sst1 and sst2 mRNA compared to those transfected with a control vector. Octreotide treatment did not alter the levels of sst1 and sst2 mRNA in either the control or gsp-transfected cells. CONCLUSION: These results suggest that GH3 cells permanently transfected with the GHRH receptor are useful in the in vitro studies on the actions of GHRH. The gsp oncogene was shown to increases the levels of sst1 and sst2 mRNA in GH3 cells, but these findings are unlikely to be the major mechanism by which gsp-positive pituitary tumors show a greater response to somatostatin. The discrepancy between the in vivo and these in vitro results should be examined further.
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Gene Expression of the Somatostatin Receptors, Gi2 alpha and Pit-1 alpha in GH3 Cells Permanently Transfected with a Mutant Gs alpha Gene.
Cheol young Park, In myung Yang, Eun hee Kim, Sook jin Sohn, Mee sook Ryu, Jeong taek Woo, Sung woon Kim, Jin woo Kim, Young seol Kim, Young kil Choi, Seung joon Park
J Korean Endocr Soc. 2002;17(2):170-182.   Published online April 1, 2002
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AbstractAbstract PDF
BACKGROUND
Cyclic AMP stimulates the expression of the somatostatin (SRIF) receptor (sst1-5) and human growth hormone (GH)-secreting pituitary tumors with the gsp oncogene which increases intracellular cAMP levels, and shows a good inhibitory response of the GH to SRIF. Taken together, we hypothesized that the gsp oncogene may increase the SRIF receptor expression or and factors related to the postreceptor signal transduction of the SRIF, in order to enhance its responsiveness to SRIF. To test this hypothesis, we investigated if the gsp oncogene could increase the sst1, sst2, Gi2 alpha, and pit-1 alpha gene expression in GH3 cells. METHODS: GH3 cells were permanently transfected with the plasmid expressing Gs alpha gene, where the arginine of codon 201 was replaced with histidine. Intracellular cAMP levels and GH concentrations were measured by radioimmunoassays. Gene expressions of the sst1, sst2, Gi2 alpha, and pit-1 alpha were determined by RT-PCR. RESULTS: Intracellular cAMP levels and medium GH release were increased by 1.7 and 2.7-fold in GH3 cells expressing the gsp oncogene, respectively. In GH3 cells expressing the gsp oncogene, the sst1 mRNA levels were decreased, whereas those of the sst2, Gi2 alpha and pit-1 alpha mRNA were increased. A 4-h forskolin (10 M) stimulation remarkably increased the sst1 and sst2 mRNA levels in GH3 cells expressing wild and mutant Gs alpha . However, forskolin did not affect the Gi2 alpha and pit-1 alpha mRNA levels. In contrast, SRIF (1 M, 2 h) decreased the sst2 mRNA levels only in GH3 cells expressing the gsp oncogene. CONCLUSION: These results suggest that higher expressions of sst2, Gi2 alpha, and pit-1 alpha, induced by the gsp oncogene may be a mechanism by which gsp-positive pituitary tumors show a greater response to SRIF. The discrepancy between these and in vivo results should be explored further.
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Gene Expression of Somatostatin Receptor (Subtype 2 & 5), Gi2 alpha and Pit-1 in GH-secreting Pituitary Adenomas.
Mee sook Ryu, In myung Yang, Cheol young Park, Jeong taek Woo, Sung woon Kim, Jin Woo Kim, Young seoul Kim, Young kil Choi, En hee Kim, Seung joon Park, Kook gi Kim
J Korean Endocr Soc. 2002;17(2):158-169.   Published online April 1, 2002
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AbstractAbstract PDF
BACKGROUND
Mutation of Gs protein subunit (gsp oncogene), detected in about 30~40% of growth hormone (GH)-secreting pituitary tumors, is associated with an increased long-acting somatostatin analog octreotide sensitivity. However, the mRNA expression of somatostatin receptor (sst) was not changed in the GH-secreting pituitary tumor, regardless of whether they were gsp oncogene positive or negative. This suggests that the expression of genes coding for Gi2 alpha , Pit-1 and the other factors involved in the regulation of secretory activity in somatotrophs is likely to be altered in gsp oncogene positive tumors. We observed the impact of the gsp oncogene on the expression of the genes coding for Gi2 alpha, Pit-1 and sst (2&5) in GH-secreting pituitary tumors. METHODS: The GH response to octreotide was examined in 13 acromegalic patients before transsphenoidal adenomectomy. Genomic DNA and RNA were extracted from fresh frozen tumor tissues. PCR was performed to amplify and sequence the region between codon 184 and 251 that includes exons 8 and 9 of the Gs gene. Sst2, sst5, Gi2 alpha and Pit-1 mRNA levels were measured by semi-quantitative RT-PCR. RESULTS: Sst2 and sst5 mRNA transcripts were detected in all tumors (7 gsp +, 6 gsp-). The amount of sst transcripts varied considerably varied between the tumors. There were no significant differences in sex, age, tumor size, grade or basal GH levels. Pit-1 and sst2 mRNA levels were not different. In contrast, Gi2 alpha mRNA levels were significantly higher in gsp (+) while sst5 mRNA levels were higher in gsp (-). CONCLUSION: These data suggests that gsp oncogene may increase Gi2 alpha levels but decrease sst5 mRNA levels. However, Pit-1 and sst2 mRNA expression may not be affected by gsp oncogene. The increased expression of the Gi2 alpha gene might be an inhibitory compensatory response to the action of gsp oncogene.
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Lanreotide Therapy in Graves' Ophthalmopathy.
Il Seong Nam-Goong, Eun Ju Lee, Jung Hwoon Kim, Jong Chul Won, Woo jae Lee, Jung Hee Han, sung Jin Lee, Sang Wook Kim, Moo Kon Son, Ho Hye Lee, Il Min Ahn
J Korean Endocr Soc. 2001;16(1):18-25.   Published online February 1, 2001
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AbstractAbstract PDF
BACKGROUND
Graves' ophthalmopathy (GO) is an autoimmune process that affects the orbital tissues. Patients with GO are usually treated with high doses of corticosteroids, retrobulbar irradiation, or by surgical decompression, however, those have some adverse effect. Recently, a synthetic somatostatin analogue has been reported for the treatment of GO. This study was performed prospectively to evaluate the therapeutic effects of lanreotide, a potent long acting synthetic somatostatin analogue, in patients that have GO. METHODS: Eight patients with moderate to severe GO (M:F=1:7, age 39.0+/-11.8 years) were included. Patients who had been treated with other modalities than GO, or had a systemic illness such as diabetes were excluded. Eight patients were given lanreotide, 40mg IM every 2 weeks over a period of 8 weeks. Their therapeutic responses were evaluated using an orbital CT or MRI and by ophthalmologic examinations. RESULTS: After 8 weeks' of lanreotide treatment, 4 patients showed decreased scores in the NOSPECS classification (p=0.059) as well as 5 patients in their clinical activity scores(p=0.109). All of the 8 patients showed improvements according to clinical evaluation criteria (p=0.008). Significant changes in the thickness of both the lateral rectus and superior rectus muscles were observed (p<0.05). No patient showed serious adverse effects related to lanreotide therapy during the follow-up periods. CONCLUSION: We conclude that lanreotide therapy has clinical benefits and show radiologic improvements in GO. Considering the minimal side-effects of lanreotide compared to those of corticosteroid, lanreotide therapy should be considered for use in selected patients that have Graves' ophthalmopathy
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Effect of Acute Hyperglycemia - and Isoproterenol - induced Hypothalamic Somatostatin Release on the Thyroid Hormone Releasing Hormone - induced Thyroid Stimulating Hormone Secretion.
Cheol Young Park, In Myung Yang, Seung Joon Oh, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi
J Korean Endocr Soc. 2000;15(4-5):486-492.   Published online January 1, 2001
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BACKGROUND
Acute hyperglycemia stimulates somatostatin (SRIH) release from the hypothalamus, and which in turn suppress growth hormone (GH) secretion and thyroid stimulating hormone (TSH) from the anterior pituitary gland. Beta-adrenergic pathway is known to stimulate the hypothalamus SRIH release. Recently, We demonstrated that isoproterenol, a beta-adrenergic agonist, had an additional suppressive effect on the suppression by glucose of GHRH-stimulated GH response. Therefore, the present study aimed to determine whether isoproterenol has an additional suppressive effect on the suppression by glucose of TRH-stimulated TSH response. METHODS: Seven healthy young men, aged 24 to 27 years, were studied. Four different TRH stimulation tests were carried out. (Test 1) TRH (Hoechst AG, Germany), 200 microgram bolus, was given intravenously at 0 minute. (Test 2) Glucose, 100 g, was given orally 30 min before TRH administration. (Test 3) Isoproterenol(Isuprel, Sanofi Winthrop, USA), 0.012 pg/kg, was infused continuously for 120 min after TRH administration. (Test 4) After pretreatment with glucose as Test 2, isoproterenol and TRH were administered as Test 3. RESULTS: Oral glucose ingestion significantly suppressed the TRH-stimulated TSH secretion. Isoproterenol infusion significantly suppressed the TRH-stimulated TSH secretion. Glucose-induced suppression of the TSH response was significantly greater than that by isoproterenol. 1soproterenol infusion after glucose pretreatment did not show any additional suppressive effect on the glucose-induced suppression of TSH response to TRH. CONCLUSION: The results suggest that isoproterenol infusion in addition to glucose pretreatment before the TRH stimulation test is not necessary for the development of stronger stimulation test for the hypothalamic somatostatin secretion.
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Effect of Gs alpha Gene Mutation on the Expression of the Rat Somatostatin Receptor Gene.
I M Yang, S J Park, H G Jhang, G J Lee, S J Oh, S W Kim, J W Kim, Y S Kim, Y K Choi
J Korean Endocr Soc. 1999;14(4):657-666.   Published online January 1, 2001
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BACKGROUND
The growth hormone (GH)-secreting pituitary adenoma with mutation of Gs alpha gene (gsp oncogene) is known to show a higher response to somatostatin. The mechanism for the higher response is unclear. We previously demonstrated that transcription of the rat somatostatin receptor (SSTR) gene was increased by cAMP. Therefore, we investigated whether the mutation of Gs alpha gene can increase SSTR gene expression. METHODS: The mutant Gs alpha expressing plasmid of which arginine of codon 201was replaced with histidine was transfected transiently and permanently into GH3 cells. cAMP and rat GH were measured by radioimmunoassay. mRNA expression of the rat SSTR2 was determined by a semiquantitative RT-PCR. RESULTS: The intracellular cAMP production was increased by 1.8 folds in the transiently transfected cells and by 1.5 folds in permanently transfected cells compared to those in the cells transfected with the vehicle plasmid, plasmid expressing the wild type or the plasmid expressing the silent mutant of codon 226. The transcriptional activation by cAMP response element of somatostatin.gene was also increased by 2 folds 24 hours after transient transfection and by 3.5 folds in the permanently transfected cells. The transcriptional activation was not enhanced by forskolin in the transiently transfected cells, whereas it was more remarkably inhibited by somatostatin compared to that in the other transfected cells. The expression of SSTR2 was increased by 1.8 folds 24 hours after transfection in the transiently transfected cells and by 3 folds in the permanently transfected cells, and it was not enhanced by forskolin and isobutylmethylxanthine. The secretion of GH from the transiently transfected cells was not significantly higher than that from the wild type-expressing cells, but it was higher in the permanently transfected cells. The suppression of GH by somatostatin was more prominent in the permanently transfected cells compared to the other transfected cells. CONCLUSION: This study suggests that a higher expression of SSTR induced by the mutant Gs alpha may be a mechanism by which gsp-positive adenomas showed a higher response to somatostatin.
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SR (Slow-Replase) Lanreotide Treatment in Acromegalic Patients.
Jae Hyun Nam, Sung Kil Lim, Sun Ho Kim, Chul Woo Ahn, Song Chul Lee, Young Duk Song, Kyung Rae Kim, Hyun Chul Lee, Ki Hyun Park, Kap Bum Huh
J Korean Endocr Soc. 1999;14(3):472-482.   Published online January 1, 2001
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BACKGROUND
Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treattnent of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid repeated sc injections or continuous sc infusions. The objective of this study was to determine the tolerability and effectiveness of the slow release (SR) somatostatin analog, SR lanreotide in active acromegaly. METHOD: Between March 1998 and May 1998, 10 patients were recruited in the prospective study carried out at Yonsei University. The effects of 6 weeks of SR lanreotide, given every 14 days at a dosage of 30 mg, im, were analyzed. All the patients completed the 6-week period of therapy. RESULTS: SR lanreotide injection produced 45% suppression of area under the curve of GH levels from the basal value on oral glucose tolerance test(OGTT). GH values on OGTT were normalized (< 2ng/mL) in 30% of patients after 6 weeks, whereas insulin-like growth factor I (IGF-I) levels were normalized in 50% of patients. No correlation was found between pretreatment GH levels and GH response to SR lanreotide or between changes in GH and IGF-I during therapy, The significant differences in response to SR lanreotide were shown between the patients with residual mass and no visible mass. During treatment, there was the significant reduction in the percentage of patients complaining of joint pain, hyperhydrosis, and paresthesias. Changes in soft tissue swelling were documented by a significant decrease in the diameter of fingers. Mild diarrhea and fatigue were the most frequent side-effects (20 30%) when SR lanreotide therapy was started. However, these side effects decreased progressively. Significant changes were noted in carbohydrate tolerance. CONCLUSIONS: These data indicate that SR lanreotide at a dose of 30 mg, im, every 14 days is an effective treatment in most unselected acromegalic patients, especially in patients with no visible mass. Tolerability to SR lanreotide therapy is high. The use of a new sustained release formulation of somatostatin analog is clearly advantageous in improving patient compliance with medical treatment for acromegaly.
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The Effect of Slow Release Lanreotide in Korean Acromegalic Ratients.
Sang Hwa Kim, In Myung Yang, Kwang Sik Seo, Eul Soon Im, Seung Joon Oh, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Sun Woo Kim, Young Kil Choi
J Korean Endocr Soc. 1999;14(3):458-471.   Published online January 1, 2001
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BACKGROUND
Previous studies have shown that somatostatin analogues such as octreotide are effective in suppressing GH and IGF-I levels in acromegaly. The recent availability of slow release lanreotide could avoid the inconveniences associated with either repeated subcutaneous injections or continuous infusions. We investigated the effects of the SR-lanreotide on clinical, biochemical and safety responses in five patients with acromegaly. And we investigated whether the response of the GH level to acute adrninistration of octreotide predicts the response after 12 weeks of treatment with the SR-lanreotide and whether the identification of gsp oncogene could be used as a therapeutic and prognostic clue in treatment with the SR-lanreotide. METHODS: We studied the effects of SR-lanreotide 30 mg administered intramuscularly biweekly for 12 weeks in five Korean acromegalic patients. Subjective improvements in the clinical symptoms of acromegaly and adverse reactions were recorded. During SR-lanreotide treatment, serum GH, IGF-I and IGFBP-3 concentrations were evaluated just before the next injection of the SR-lanreotide. Before the start of SR-lanreotide therapy the sensitivity of GH secretion to the octreotide was tested by measuring the effect of the acute response to 0.1 mg intravenously on plasma GH levels followed until 6 hours after administration of octreotide. Direct polymerase chain reaction sequencing of the gsp oncogene were performed. We compared the responses to SR-lanreotide in patients harboring gsp-positive and gsp-negative somatotroph adenomas. RESULTS: The treatment with SR-lanreotide for 12 weeks could suppress the GH level by more than 50% in four of five patients and normalize the IGF-I in two patients. No correlation was found between the GH level and IGF-I level at the end of the study. The IGFBP-3 level correlated with the IGF-I level in three of five patients. Although the initial GH response to octreotide tended to correlate with the IGF-I response after SR-lanreotide treatment, the results were statistically insignificant. The patients with gsp-positive tumor tended to show a better response to SR-lanreotide. During treatment, there was a reduction in the percentage of patients complaining of joint pain, fatigue, digital paresthesia, and hyperhydrosis. Changes in soft tissue swelling were documented by decreases in finger circumference. The common adverse events were abdominal discomfort, loose stool, and diarrhea. These events were decreased progressively. No patients discontinued the treatment of SR-lanreotide due to adverse events. CONCLUSION: This study showed that SR-lanreotide is effective in controlling acromegalic symptoms as well as GH and IGF-I hypersecretion. This treatment was well tolerated and more convenient for the patients. Further studies are required for clinical outcome of long-term SR-lanreotide treatment and cost-effective analysis.
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Case Report
A Case of Diabetes Mellitus Caused by Calcitonin and Somatostatin Secreting Pancreatic Islet Tumor.
Jae Hoon Chung, Kwang Won Kim, Byoung Joon Kim, Sung Hoon Kim, Kyung Ah Kim, Myung Sik Lee, Moon Gyu Lee, Yong Ki Min, Jong Ryol Ham, Dong Joon Kim, Hoe Jung Lee, Young Ryoon Oh
J Korean Endocr Soc. 1999;14(2):425-431.   Published online January 1, 2001
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A case of 39-year-old diabetic patient with a calcitonin and somatostatin secreting pancreatic islet tumor is presented. He had suffered from chronic diarrhea and dyspepsia for 10 years and was diagnosed with diabetes 2 years ago. Abdominal CT revealed a huge abdominal mass which was considered as a neuroendocrine tumor after US-guided needle biopsy. A distal pancreatectomy and splenectomy were performed. Histologically, tumor cells, amanged in solid sheets, showed small nuclei without significant atypia and granular eosinophilic cytoplasm. Tumor cells showed strong immunoreacitivity for calcitonin and somatostatin. The serum clacitonin was markedly elevated (268.7 pmol/L, normal range; 0.9-7.6 pmol/L). After resection of the tumor, diarrhea and dyspepsia diappeared, and oral glucose tolerance test showed normal glucose tolerance with normalization of calcitonin.
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Endocrinol Metab : Endocrinology and Metabolism
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