Endocrinology and Metabolism

Original Articles

A Study of Point Mutations of Human Insulin-like Growth Factor - 1 (IGF - 1) Promoter Gene in Familial Short Stature (FSS) Patients.: In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Hyun Ha Chang, In Kyung Jung, Tae Kwan Park; J Korean Endocr Soc. 1996;11(4):500-509. Published online November 7, 2019

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Abstract PDF: Background
FSS is a normal variants in Korea, but some of them had defect of noctumal GH pulse i.e. neurosecretory dysfunction. Although Korean children had strikingly got higher final height in the last decade. We are interested in what kinds of differences were existed in FSS group. Previous study showed theres no difference of GH related biochemical markers between normal and FSS group, like IGF-I, IGFBP-3 etc. We analyzed molecular difference in FSS group. Methods: We screened 23 FSS patients and 16 normal controls to IGF-I gene prornoter region with PCR-SSCP (single strand conformation polymorphisrn) method and sequenced 1 FSS patients who had abnormal SSCP band. Results: We found 1 out of 23 patients with abnormal SSCP band (none for 16 controls). Their IGF-I promoter gene were sequenced with modified Maxam-Gilbert method. One subject had 2 point mutations(+8 and +74). Conclusion: We found point mutations of IGF-I promoter in FSS group, This position was regarded as HNF(hepatic nuclear factor)-3 binding sites. We needed more study for the detection of its biological function according io linear growth with in vivo and in vitro study.

Effect of Dexamethasone and Deflazacort on the Function and Gene Expression of the Primary Cultured Human Osteoblast-Like Cells.: Hyun Koo Yoon, In Myung Yang, Sung Woon Kim, Soung Seol Kim, Young Kil Choi, Ho Yeon Chung, Young Soon Kang, In Gul Moon, Chang Hoon Yim, Sang Woo Kim, Ki Ok Han, Hak Chul Chang, In Kwon Han; J Korean Endocr Soc. 1996;11(4):479-491. Published online November 7, 2019

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Abstract PDF: Background
Chronic use of glucocorticoid is known to result in osteoporosis. Deflazacort (DFZ), a synthetic glucocorticoid, has been reported to have bone sparing properties in vivo eompared to dexamethasone(DEX). Not only the direct effect of DFZ on human osteoblast but the mechanism by which the drug spares bone remains unclear. This study, therefore, is aimed to investigate the direct effect of DFZ on the proliferation and differentiation of human osteoblast as well as on the gene expression of osteocalcin and osteoblast as well as on the gene expression of osteocalcin and growth factor produced in osteoblast. Methods: Human osteoblast-like cells were cultured from a piece of the tibia removed during selective orthopedic surgery for patients without metabolic bone diseases. The morphological iden- tification of osteoblast-like cell was performed under the light microscope after alkaline phosphatase staining. Cell proliferation rate was determined by [3H] thymidine incorporation into DNA. Cell differentiation was determined by alkaline phophatase activity. mRNA expression was quanti- tatively measured by the competitive reverse transcription-polymerase ehain reaction(RT-PCR). Results: The cultured cells demonstrated 1,25-dihydroxyvitamin D3-induced increases in alkaline phophatase activity and osteocalcin mRNA expression which are the properties of osteoblast. Twenty six percent of the cultured cells were identified as osteoblast-like cells by alkaline phophatase staining. After 24hr incubation with DEX or DFZ, the [3H) thymidine incorporation was significantly inhibited by 100nM DEX or DFL Alkaine phophatase activity was significantly increased by 100nM DEX. Osteocalcin mRNA was significantly decreased by both glueocorticoids. While DEX significantly suppressed expression of asteocalcin mRNA at 10nM and 100nM, DFZ did so only at 100nM. IGF-I mRNA was significantly decreased by 100nM DEX. Conclusion: These results suggest that the inhibitory effect of DFZ on the cell proliferation and protein synthesis is less than that of DEX, which might be responsible for the bone sparing effect of DFZ in vivo.

Expression of Exon 1 and 6 of Indulin-like Growth Factor - 1 (IGF - 1) Gene in Thyroid Tissues.: Sung Woon Kim, Hyun Ha Chang, In Kyung Jung, Jeong Taek Woo, In Myung Yang, Jin Woo Kim, Soung Seol Kim, Young Kil Choi; J Korean Endocr Soc. 1996;11(4):409-417. Published online November 7, 2019

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Abstract PDF: Background
Goiter has been a common problem in the thyroid disease. The exact mechanism of goiter had not been clarified yet, but some goiters were increased with TSH(thyrotropin releasing hormone) dependent manner. TSH might be a major influencing factor for increasing size of goiter(goitrogen) and theres many cofactors those influenced to goiter size. One of the rnost prominent growth factor as a goitrogen is a IGF-I(insulin-like growth factor-I). IGF-I play a great role as a cofactor of goitrogen with TSH. This study, therefore, is aimed to investigate intracellular activation of IGF-I gene promoter in the surgical specimens of thyroid tumor. Methods: We used surgical specimen of various thyroid tissues from normal to malignant along its cell nature. Actually we used normal liver tissue as a IGF-I control tissue, normal thyroid, benign adenoma, and papillary thyroid cancer tissue with its malignat nature. We checked Mrna expression of whole IGF-I and IGF-I exon 6 by Northern blot method, and IGF-I, promoter 1 expression by RT-PCR-transcription method. Autoradiographied signals were analysed with densitometer. Results: We found whole IGF-I mRNAs were expressed with alternate splicing in exon 1, 2 and exon 4, 5 respectively. Striking events of IGF-I transcription were multiple tranascription initiatian in Pl and P2, and 3 sites for polyadenylation in exon 6. Four or more Mrna bands in Northern blot analysis of IGF-I(0.8, 1.4, 4.2, and 7.8kb) were noted. In low molecular weight IGF-I Mrna did not change their signal intensity with tissues, but exan 6(7.8kb) signals were significantly increased to its hepatic expression levels in malignant tissue. IGF-I, exon 1 expression by RT-PCR-T7 transcription was strikingly increased in thyroid cancer tissue, but exon 6 expression was not a great expession. Conclusion: One possible guess for this expression discrepancy of each exon may be originated from different Mrna degradation of each IGF-I signals. We need more preeise experiment for Mrna degradation speed of IGF-I.

Ca Effects on Synthesis and Secretion of Insulin-like Growth Factor(IGF-I) and IGF-Binding Proteins by the Perfased Rat Liver.: Dae Yeol Lee, Chang Won Kang, Jung Soo Kim; J Korean Endocr Soc. 1996;11(2):189-198. Published online November 7, 2019

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Abstract PDF: Background
The insulin-like growth factors, IGF-I and -II, are important metabolic factors involved in cell growth and metabolism. The IGFs are produced in most organs but the liver is believed to be the principal source of circulating IGF-I. It has been demonstrated that calcium in the extracellular fluid has effects on the secretion of various hormones such as parathyroid hormone, insulin and atrial natriuretic peptide in variety of tissues. Methods: In arder to investigate that liver produce IGF-1 and IGFBP-3 and the role of calcium in the regulation of IGF-I and IGFBP-3 secretion and synthesis, the rat liver perfusian model was employed. The liver was perfused with Krebs-Henseleit bicarbonate(KHB) buffer containing 0 or 2.5 mM CaC12 for 2 hours, and 4-ml fractions of perfusates were collected and determined the concentration of IGF-I and IGFBP-3 by using RIA after Sep-pak extraction and Western ligand blot. respectively. To increase or decrease the concentration of intracellular calcium, we also used EGTA, calciurn ionophore A23187 increased IGF-I secretion and synthesis in liver(18.13+0.97 vs 15.78+1.01, p<0.01). However, concentration of glucose was not significantly affected by both calcium(2.07+1.44 vs 2.24+1.74) and BGTA(2.01+1A7 vs 3.11+1.01). Conclusion: Our results demonstrate that liver is a major place far IGF-I and IOFBP-3 production and calcium specifically affects the secretion of IGF-I in the liver perfusion, suggesting that the calcium environment of hepatic cells may influence the secretion of the hepatic IGF-I.

Serum Insulin-like Growth Factor-1(IGF-1) and Insulin-like Growth Factor Binding Proteins in Hyperthyroidism and Hypothyroidism.: Hyun Mo Song, Sang Seok Park, Tae Seon Park, Hong Sun Baek, Dae Yeol Lee; J Korean Endocr Soc. 1996;11(1):52-60. Published online November 7, 2019

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Abstract PDF: Background
s: Thyroid hormones play a fundamental role in the initiation and maintenance of somatic growth in mammalian species, and the insulin-like growth factors(IGFs) occupy a position of central importance in the growth of all tissues. To evaluate the changes in serum insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding proteins in hyperthyroid and hypothyroid patients, sera was obtained from 19 hyperthyroid patients, 9 hypothyroid patients, and 10 healthy volunteers. Methods: IGF-I concentration was determined by radioimmunoassay, and changes in IGFBPs were assesed by Western Ligand Blotting. To evaluate the binding pattern of IGF-I & IGFBPs, autoradiographs were obtained. Results & Conclusion: IGF-I levels were increased significantly in hyperthyroid patients(mean ±SE, 267.88±9.80 ng/ml, p<0.05) and decreased significantly in hypothyroid patients(154.81±1.43 ng/ml, p<0.01) compaired to healthy control group(209.45±.60 ng/ml). Autoradiograph of serum IGFBPs from patients with hyperthyroidism and hypothyroidism did not show any change in the intensity of IGFBP-3 bands(40-45 KD) and IGFBP-1 bands, but in hyperthyroid patients, it showed increased intensity of IGFBP-2 band compared to healthy control group and hypothyroid patients.

Case Reports

A Case of Gastrointestinal Stromal Tumor with Recurrent Hypoglycemia.: Sun Hee Ko, Seok Hwan Kim, Il Ho Maeng, Koon Soon Kim, Yi Sun Jang, Hye Soo Kim, Jong Min Lee, Suk Young Park, Sang Bum Kang; Endocrinol Metab. 2010;25(2):125-130. Published online June 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.2.125

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Abstract PDF: Non-islet cell tumor induced hypoglycemia (NICTH) is attributable to overproduction of insulin-like growth factor-II (IGF-II) by solid tumors, and these tumors usually originate from mesenchymal or epithelial cells. Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor and most commonly find in the gastrointestinal tract. It is usually expresses the CD117 (stem cell factor receptor, c-kit) detected by immunohistochemistry. Hypoglycemia associated with GIST is very rare and this has not yet been reported in Korea. A 72-year-old man was hospitalized due to frequent episodes of confusion. It was observed that non-hyperinsulinemic hypoglycemia, an elevated serum IGF-II level and a huge liver mass. The histology of liver mass showed c-kit (CD117) positivity, which was consistent with GIST, but it was surgically unresectable. He was treated with imatinib mesylate. Although he recieved palliative treatment, he still experienced intermittent fasting hypoglycemia. After 2 months, the serum IGF-II level was even higher than before. We changed imatinib mesylate to sunitinib malate and performed radiotherapy on the liver mass. Although the change of the liver mass was not significant, he did not suffer from hypoglycemia for three months afterwards.

A Case of Non-islet Cell Tumor Hypoglycemia.: Yun Tae Chae, Il Jun Hwang, Kyung Hee Ryu, Eun Hyang Ko, Jung Im Rue, Soo Kyung Kim, Seok Won Park, Yoo Ri Kim, Yong Wook Cho, Young Kil Choi, Sang Jong Lee; J Korean Endocr Soc. 2006;21(1):74-78. Published online February 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.1.74

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1 Crossref

Abstract PDF

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.

Citations

Citations to this article as recorded by

A Case of Epithelioid Hemangioendothelioma of the Pelvic Retroperitoneum with Hypoglycemia
Ji Ryang Kim, Yun Kyung Jeun, Kee Tae Park, Yang Ho Kang, Seok Man Son, In Ju Kim, Yong Ki Kim, Kyung Un Choi, Kwang Jae Lee
Journal of Korean Endocrine Society.2007; 22(6): 440. CrossRef

Original Article

The One Year Effects of Growth Hormone Replacement on the Body Composition in the Normal Adults.: Eui Hyun Kim, Suk Chon, Kwan Pyo Koh, Seong Joon Oh, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim; J Korean Endocr Soc. 2004;19(4):303-319. Published online August 1, 2004

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Abstract PDF: BACKGROUND
The secretion of growth hormone [GH] declines by 14.4% every decade, leading to the suggestion that the elderly are functionally GH deficient, which may increase adipose tissue and decrease the bone mass and density, as well as other negative changes in body composition. Recently, many studies have shown that GH replacement therapy may restore the changes that occur in the body composition with aging. AIM: The GH and insulin like growth factor-I[IGF-I] profiles were identified during GH replacement therapy in the elderly and compared with those of GH deficient[GHD] patients. The metabolic effects of GH replacement on the body composition of the elderly was also investigated, especially the body fat, muscle and bone parameters. Subjects and METHODS: 98 healthy normal out-patients and 13 GHD patients, who had peak GH concentrations less than 5 ng/mL after an insulin tolerance test [ITT] or growth hormone releasing hormone [GHRH] stimulation test, were the subjects of this study. All were receiving appropriate thyroid, adrenal and gonadal hormone replacements. The dose of recombinant human GH [rhGH] was 0.02~0.04 mg [0.06~0.12 IU]/kg of body weight.per week, given nightly by a subcutaneous injection, six times a week, over a 52 week period. The GH was measures after the ITT and GHRH stimulation tests, and the IGF-1, lipid parameters [total cholesterol, triglyceride, HDL-, and LDL cholesterol], visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], VAT/SAT ratio, quadriceps muscle area, total body fat, total bone mineral density [BMD], alkaline phosphatase [ALP], osteocalcin and urine deoxypyridinoline [DYP], as well as anthropometry, were also assessed. RESULTS: All the anthropometry features between the normal and GHD subjects were very similar. The hormonal profiles were checked; the GH peaks of the ITT and GHRH stimulation tests were significantly higher in the normal compared to the GHD patients, but the GHRH test showed lower GH peaks in than those of the ITT test in the normal subjects. The IGF-I levels after GH replacement were constantly maintained in the normal and GHD groups after 3 week and until the 52nd week. According to the lipid profiles, the GHD group showed significantly decreased total cholesterol and LDL-cholesterol after 12 weeks of GH replacement. The normal male group revealed constantly increased triglyceride levels during the entire 52 weeks of GH replacement, but thr other lipid parameters remained completely unchanged. The normal female group showed no change in any of their lipid parameters. Although the amounts of VAT at the baseline were the same in all groups, only the normal males showed effective visceral fat removal, with significantly reduced VAT after 52 weeks of GH treatment. In the normal female and GHD groups the bone mineral density had a V shaped curve after GH replacement, and the ALP and osteocalcin levels were significantly increased after 26 weeks of GH therapy in the GHD group. CONCLUSION: The body compositions in the normal male, female and GHD groups were similar before the GH replacement therapy, and the serum IGF-I levels were well maintained in all these groups during GH replacement. Although the majority of aging symptoms were improved, the body compositions tended to return to their original stati in the normal groups. GH replacement is recommended in the elderly for better health and well-being

Case Report

A Case of non-islet Cell Tumor Hypoglycemia Due to Gepatoma-increased serum subfraction of big insulin-like growth factor II.: Kwan Woo Lee, Hyun Soo Kim, Yun Suk Chung, Hyun Man Kim, Myung Ho Yoon, Joon Ho Ko, Hyo Chul Kim, Young Soo Kim, Sung Won Cho; J Korean Endocr Soc. 1997;12(4):667-671. Published online January 1, 2001

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Abstract PDF: Hypoglycemia due to non-islet cell tumor is usually associated with hypersecretion of big insulin-like growth factor II (IGF-II). This big IGF-II cannot form ternary IGF complex, and is biologically more active in peripheral tissue, inducing increased glucose utilization and hypoglycemia. A 57-year-old man developed severe hypoglycemia due to hepatocellular carcinoma. To control hypoglycemia, the patient required continuous glucose infusion. The circulating levels of cortisol and free T4 were in the normal range. The plasma levels of insulin, C-peptide, IGF-I, IGF binding protein-3 (IGFBP-3), and total IGF-II levels were decreased. Radioimmunoassay of IGF-II revealed that big IGF-II immunoreactivity markedly increased compared to that of normal control. In this patient, it was strongly suggested that big IGF-II might be a cause of severe intractable hypoglycemia.

Original Article

Characteristics of Serum Insulin-like Growth Factor ( IGF ) and IGF-Bindign Protein-3 during Pregnancy.: Dae Yeol Lee, Jung Soo Kim, Hong Ro Lee, Cheol Hee Rhee, Soo Chul Cho; J Korean Endocr Soc. 1997;12(3):376-385. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Pregnancy in human and rodents is associated with dramatic matemal metabolic changes. Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum IGF-binding protein (IGFBP-3) which regulates the availability of the IGFs to their specific target tissues. METHODS: To examine the changes of IGFs and IGFB-3 during pregnancy, we measured serum total IGF-I, free IGF-I, IGF-II and IGFBP-3 by using specific radioimmunoassay, immunoradio-metric assay, western ligand blot and western immunoblot. Blood samples were obtained from 88 pregnant women between 6-40 weeks gestation. RESULTS: While serum IGF-I levels increased up to 50% in late pregnancy, serum IGF-II levels remained unchanged. However, serum free IGF-I levels were significantly higher during pregnancy than in nonpregnancy. Western ligand blot analysis revealed that IGFBP-3 in pregnancy serum was significantly decreased at 6 weeks of gestation, continued decreased level until term, and returned to a nonpregnant level by postpartum 10 day. Serum IGFBP-3 profiles in Western immunoblot analysis revealed that 30 kDa fragments of IGFBP-3 were detectable in pregnancy serum but not in nonpregnancy serum. In contrast, serum IGFBP-3 levels using radioimmunoassay was significantly increased in late pregnancy. CONCLUSIONS: 1) serum IGF-I was significantly elevated in late pregnancy 2) serum IGF-II was not significantly changed 3) free IGF-I significantly elevated throughout gestation 4) intact IGFBP-3 was markedly reduced after 6 weeks of gestation.

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