Endocrinology and Metabolism

Volume 21(3); June 2006

Review Articles

Current Research on the Structure and Function of the Growth Hormone Releasing Hormone Receptor.: Bruce Gaylinn; J Korean Endocr Soc. 2006;21(3):173-183. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.173

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Abstract PDF: Growth hormone releasing hormone receptor (GHRH-R) is a family B1 G-protein coupled receptor found predominantly on pituitary somatotrophs. In the adults it is required for the normal synthesis and release of growth hormone (GH) from the pituitary. During development it is required for the normal proliferation and maturation of somatotrophs within the pituitary. Mutations of this receptor in mouse and man are associated with GH deficiency, short stature and pituitary hypoplasia. This signaling system plays important roles in growth and development, metabolism of muscle and fat, and is implicated in the regulation of cardiac and immune function, wound healing, tumor growth and the aging process. Current areas of active research discussed here include: studiesof the structure of the receptor binding site and its interaction with GHRH, alternative splice variants of the GHRH-R which appear to promote tumor proliferation, truncated receptor isoforms that act as dominant negative inhibitors of wild type receptor, and the unclear physiologic role of the GHRH system in birds and fishes.

Translational Research Using Sodium/Iodide Symporter.: June Key Chung, Joo Hyun Kang; J Korean Endocr Soc. 2006;21(3):184-188. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.184

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Abstract PDF: No abstract available.

Editorial

RANK-Fc Gene Therapy in Mouse Model of Osteoporosis.: Ho Yeon Chung; J Korean Endocr Soc. 2006;21(3):189-191. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.189

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Abstract PDF: No abstract available.

Original Articles

Retrovirus Mediated Gene Transfer of RANK-Fc Ameliorates Bone Loss in a Mouse Ovariectomy Model of Osteoporosis.: Dohee Kim, Chan Soo Shin; J Korean Endocr Soc. 2006;21(3):192-203. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.192

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Abstract PDF

BACKGROUND
Interactions between the receptor activator of the NF-kappaB ligand (RANKL) and its receptor, RANK, are important in the terminal differentiation and activation of osteoclasts. In the current investigation, we examine the feasibility of using genetically modified mesenchymal stem cells (MSCs), C3H10T1/2 cells as a platform for the sustained systemic delivery of therapeutic proteins into the circulation in an osteoporosis model, and investigate retroviral-mediated gene therapy of RANK-Fc as a means of ameliorating ovariectomy (OVX)-induced bone resorption. METHODS: C3H10T1/2 cells were transduced with a MSCV-based retroviral vector containing cDNA of a fusion protein combining the extracellular domain of murine RANK with the human immunoglobulin constant domain (MSCV-RANK-Fc-eGFP). Young adult female mice were subjected to OVX or sham surgery, followed by treatment with transduced cells or PBS 4 weeks later. The expression of RANK-Fc by these cells was assessed, both in vitro and in vivo. Total bone mineral density (BMD) was measured and GFP expression was examined. RESULTS: Transduced cells produced biologically active RANK-Fc in vitro and in vivo. Mice that were subjected to OVX followed by treatment with cells transduced with MSCV-RANK-Fc-eGFP 4 weeks later contained no significant but higher total BMD than either the control vector or PBS-treated mice after 8 weeks. Higher GFP expression was attained in the liver, spleen, and intra-abdominal fat of mice treated with MSCV-RANK-Fc-eGFP. CONCLUSION: The data collectively indicate that C3H10T1/2 cells are effectively transduced with a MSCV-based retrovirus, and are capable of secreting biologically active RANK-Fc in vitro and in vivo. Moreover, gene therapy facilitating the sustained delivery of RANK-Fc may be an effective method to reverse OVX-induced osteoporosis.

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RANK-Fc Gene Therapy in Mouse Model of Osteoporosis
Ho Yeon Chung
Journal of Korean Endocrine Society.2006; 21(3): 189. CrossRef

Analysis of the Pharmacokinetics of Recombinant Human TSH in Patients with Thyroid Papillary Carcinoma.: Tae Sik Jung, Hye Seung Jung, Jung Hwa Jung, Yun Jae Chung, Eun Young Oh, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2006;21(3):204-212. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.204

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Abstract PDF

BACKGROUND
Individual variations of the pharmacokinetics of recombinant human TSH (rhTSH) might influence the efficacy of the radioactive iodine (RAI) uptake. We studied to investigate the individual pharmacokinetics of rhTSH and the effect of the anthropometric parameters on the serum TSH levels in patients with thyroid papillary carcinoma. METHODS: We selected 16 patients with conventional rhTSH administration for the preparation of RAI administration between June 2004 and May 2005. We measured serum TSH levels at 24-hour (prior to second rhTSH injection), 48-hour (peak level, prior to RAI administration) and 96-hour (prior to scanning) after the first rhTSH injection. We analyzed the correlation of each TSH levels with age, height, weight, creatinine clearance, body mass index (BMI), and body surface area (BSA). RESULTS: Peak TSH levels were negatively correlated with weight, BMI, and BSA. Among them, weight was an independent parameter by multivariate analysis. Decrement of serum TSH levels from the peak to the level at 96-hour was negatively correlated with weight, BMI, and BSA. It was positively correlated with increment of serum TSH levels from the level at 24-hour to the peak level. Serum TSH level at 96-hour was lower than 25 mU/L in nine of 16 patients. CONCLUSION: Body weight was inversely correlated with peak TSH level after rhTSH administration. rhTSH-stimulated TSH levels might be exaggerated to unwanted levels, and very rapidly degraded in lower-weighted patients. We should make up for the rhTSH regimen considering the individual variations of its pharmacokinetics.

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Efficacy of Low-dose and High-dose Radioactive Iodine Ablation With rhTSH in Korean Patients With Differentiated Thyroid Carcinoma
Ji Young Joung, Ji Hun Choi, Yoon Young Cho, Na Kyung Kim, Seo Young Sohn, Sun Wook Kim, Jae Hoon Chung
American Journal of Clinical Oncology.2016; 39(4): 374. CrossRef

The Relationship of Ghrelin and Leptin with the Biochemical Markers for Adult Growth Hormone Deficiency.: Chan Hee Jung, Eun Jung Rhee, Se Yeon Kim, Ki Won Oh, Won Young Lee, Sun Woo Kim; J Korean Endocr Soc. 2006;21(3):213-221. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.213

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Abstract PDF: BACKGROUND
In spite of the increasing information that has recently been accumulated on the involvement of ghrelin and leptin in energy balance control, the relationship between ghrelin or leptin and the growth hormone (GH)-Insulin like growth factor-1 (IGF-1) axis in the pathological condition characterized by growth hormone deficiency (GHD) has been poorly clarified. Therefore, we performed this study to evaluate the correlation of the plasma levels of ghrelin and leptin with the anthropometric and biochemical markers in GHD adults and also in healthy adults. METHODS: For the 60 male adults (GHD, n = 12; healthy control, n = 48; average age, 54 years), we investigated the correlations between the serum leptin and ghrelin levels with the anthropometric and biochemical factors in the two groups, as divided by their GH status. The diagnosis of GHD was made on the basis of a peak response for serum GH of less than 5 micro/L to a GH provocative test (L-dopa test). All the subjects underwent assessment of waist circumference, BMI and percentage body fat for their body composition. The plasma ghrelin, leptin, insulin, GH and IGF-1 were measured. RESULTS: The groups were well-matched for their age, BMI, waist circumference and percentage of body fat. The ghrelin and leptin levels were not significantly different between the two groups. There was no correlation between the peak GH level or the area under the curve of growth hormone (GHAUC) and the ghrelin concentrations in the GHD subjects. Plasma leptin correlated positively with the percentage of body fat, the total cholesterol and the LDL-cholesterol, but it had no correlation with the peak GH or GHAUC in the GHD subjects. CONCLUSIONS: It is possible that the ghrelin concentrations appeared normal in the GHD subjects. Further studies are needed to clarify these controversies about the relation of ghrelin and leptin with the GH and IGF-1 levels.

The Effect of Oxidative Stress on the Proliferation and Differentiation of Human Bone Marrow Stromal Cell-Derived Osteoblasts.: Eun Sook Oh, Ki Hyun Baek, Won Young Lee, Ki Won Oh, Hye Soo Kim, Je Ho Han, Kwang Woo Lee, Ho Young Son, Sung Koo Kang, Moo Il Kang; J Korean Endocr Soc. 2006;21(3):222-232. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.222

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Abstract PDF

BACKGROUND
The objectives of our study were to assess the effects of oxidative stress on the proliferation, differentiation and apoptosis of human bone marrow stromal cell (BMSC)-derived osteoblasts and to explore pathways by which osteoblast cell apoptosis was induced. METHODS: Mononuclear cells including BMSCs were cultured to osteoblastic lineage. Different doses of hydrogen peroxide (H2O2) were added to the culture media. The colony forming units-fibroblastic (CFU-Fs) were stained with crystal violet and alkaline phosphatase (ALP). The MTT assay was done to see the effect of H2O2 on cell viability. The effect of H2O2 on osteocalcin gene expression was determined by RT-PCR. The matrix calcification measurement was performed. FACS analysis was performed to determine the osteoblasts apoptosis. Caspase-3, -8 and 9 activity assay and cytochrome c release were measured. RESULTS: The size and number of ALP (+) CFU-Fs were also decreased by H2O2 treatment. When compared with the control group, H2O2 significantly decreased the total number of cells of each culture well during MTT assay. H2O2 significantly diminished expression of osteocalcin mRNA. N-acetylcystein (NAC) blocked the diminution of cell viability and the inhibition of osteocalcin mRNA expression by H2O2. H2O2 reduced matrix calcification. FACS analysis revealed H2O2 increased percentage of apoptotic cells. Addition of H2O2 resulted in the increase of caspase-9 and -3 activity but not caspase-8, and release of cytochrome c to the cytosol. CONCLUSION: These data suggest that, in primary human BMSCs, oxidative stress inhibits proliferation of stromal cells and inhibits the differentiation to osteoblastic lineage. In addition, oxidative stress induces apoptosis of human BMSC-derived osteoblasts and this may be mediated by mitochondrial pathway of apoptotic signal.

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Antioxidaitve and Differentiation Effects of Artemisia capillaris T. Extract on Hydrogen Peroxide-induced Oxidative Damage of MC3T3-E1 Osteoblast Cells
Jee-Eun Seo, Eun-Sun Hwang, Gun-Hee Kim
Journal of the Korean Society of Food Science and Nutrition.2011; 40(11): 1532. CrossRef

Case Reports

A Case of Hyperthyroidism with Complete Atrioventricular Block and Cardiac Arrest.: Ho Sup Lee, Yun Suk Yang, Il Guon Jo, Sun Ik Jang, Sung Chang Jung; J Korean Endocr Soc. 2006;21(3):233-238. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.233

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Abstract PDF: The cardiovascular manifestations of hyperthyroidism are sinus tachycardia, paroxysmal supraventricular tachycardia, atrial fibrillation, atrial flutter, atrioventricular block, bundle branch block, angina pectoris, heart failure, and cardiomyopathy. Though complete atrioventricular block is rare, it is important to recognize it in clinical practice because of the possibility of cardiac arrest. We experienced a 47-year-old female patient who had hyperthyroidism with complete atrioventricular block and developed cardiac arrest despite the initiation of an antithyroid drug. We could resuscitate successfully and inserted a temporary pacemaker, but eventually a permanent pacemaker was needed to prevent the recurrence of cardiac arrest. We report a rare case of complete atrioventricular block and cardiac arrest associated with hyperthyroidism with the review of references.

A Case of Type 1 von Hippel-Lindau (VHL) Disease associated with VHL Germline Mutation.: Jeong Hoon Seo, Jae Hong Yang, Pyoung Lak Choi, Yu Lee Kim, Young Sik Choi, Yo Han Park, Ji Ho Ko, Hio Chung Kang, IL Jin Kim, Jae Gahb Park; J Korean Endocr Soc. 2006;21(3):239-244. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.239

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Abstract PDF

Von Hippel-Lindau (VHL) disease is an autosomal dominant neoplasia syndrome that result from a germline mutation in the VHL gene. Germline mutation in the VHL gene lead to the development of hemangioblastomas of the central nervous system and retina, cysts and clear cell carcinoma of the kidney, cyst adenomas of other organs, and pheochromocytoma. VHL is a tumor suppressor gene on the short arm of chromosome 3. VHL disease has been classified into two main clinical subtypes depending on the presence (type 2) or absence (type 1) of pheochromocytoma. Type 2 has been subdivided into three categories depending on the presence (type 2B) or absence (type 2A) of renal cell carcinoma, with type 2C being a rare subtype in which pheochromocytoma is the sole manifestation of VHL disease. Recently we experienced a family with VHL type 1 who carry C to T (Q73X) transition in codon 217 nonsense germline mutation in exon 1 of VHL gene. The authors report this case with literature review.

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Germline mutation of Glu70Lys is highly frequent in Korean patients with von Hippel–Lindau (VHL) disease
Sena Hwang, Cheol Ryong Ku, Ji In Lee, Kyu Yeon Hur, Myung-Shik Lee, Chul-Ho Lee, Kyo Yeon Koo, Jin-Sung Lee, Yumie Rhee
Journal of Human Genetics.2014; 59(9): 488. CrossRef

A Case of Pituitary Mucormycosis in Diabetic Patient with Acromegaly and Gastric Cancer.: Pyoung Rak Choi, Hong Jun Yu, Seung Wu Yang, Gyu Jong Kim, Hark Rim, Yu Ri Kim, Young Sik Choi, Yo Han Park, Bong Kwon Chun; J Korean Endocr Soc. 2006;21(3):245-250. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.245

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Abstract PDF

Rhino-orbito-cerebral mucormycosis (ROCM) is an uncommon, acute, and aggressive fungal infection occurring in several immunocompromised states including poorly controlled diabetes. ROCM causes a very high residual morbidity and mortality due to the angioinvasion property of the fungus. Acromegaly is a chronic condition resulting from the excessive secretion of growth hormone, generally from pituitary adenoma. Although it has been demonstrated that acromegalic patients have an increased risk of neoplasm, gastric cancer with acromegaly is very rare. We experienced a case of pituitary mucormycosis in the diabetic patient with acromegaly and gastric cancer. The patient was treated successfully with subtotal gastrectomy for early gastric cancer, transsphenoidal surgery for pituitary adenoma, and a systemic application of amphotericin B for the mucormycosis.

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Optimization of ethanol extraction and further purification of isoflavones from soybean sprout cotyledon
Seung Yong Cho, Yu Nam Lee, Hyun Jin Park
Food Chemistry.2009; 117(2): 312. CrossRef

A Case of Hyperthyroidism Associated with Symptomatic Hypercalcemia.: Ju Hyun Choi, Woo Je Lee, Yun Hee Chung, Hye Won Park, Dan Bi Lee, Jong Chul Won, Duk Jae Kim, Ghi Su Kim; J Korean Endocr Soc. 2006;21(3):251-256. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.251

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Abstract PDF: Two of the common causes of hypercalcemia are malignancy and primary hyperparathyroidism. These disorders are easily diagnosed by the clinical manifestations and measurement of the serum intact parathyroid hormone (PTH) level. On the other hand, hyperthyroidism is an uncommon cause of hypercalcemia. The diagnosis of hypercalcemia associated with hyperthyroidism can only be made by excluding the common causes of hypercalcemia and by observing the improvement of the hypercalcemia and its associated symptoms with normalizing the thyroid function. Herein we reported our experience with a 67 year-old woman who presented with nausea and vomiting. She showed elevated serum calcium and phosphorus levels. Serum intact PTH level was 1.1 pg/mL (normal range; 10~65). The results of the thyroid function test were compatible with hyperthyroidism. After resolution of the thyrotoxicosis with combination treatment of methimazol and Lugol's solution, the patient's serum calcium and phosphorus levels were normalized and the symptoms were improved.

A Case of Patient with Opioid-Induced Adrenocortical Insufficiency and Hypogonadism.: Hai Jin Kim, Chul Sik Kim, Jong Suk Park, Jina Park, Eun Seok Kang, Chul Woo Ahn, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee; J Korean Endocr Soc. 2006;21(3):257-260. Published online June 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.3.257

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Abstract PDF: Opioids are known to decrease plasma cortisol and testosterone level in human and other mammals. Nowadays, opioid use is exponentially increasing, but little is known about its side effects. With the help of progressive human science, we can habit longer life and as result, are becoming more avid for healthy life. In this respect, analgesics play important role in maintaining good and healthy quality of life. For this reason, it is important to fully understand its side effects and handle it with special precaution. We are reporting a 22-year-old male who had been taken opioid analgesic for more than six years to relieve chronic, intractable headache. Then, his hormone test revealed hypogonadotropic hypogonadism combined with hypoadrenocorticotropic hypoadrenalism but showed no definite clinical features except for sexual frigidity. After two years of oxycodon discontinuation, we reevaluated that his hormone test, and all other laboratory tests returned to the normal range.

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