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Volume 12(2); June 1997
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Original Articles
Present Stutus and Perspectives of Androgen Replacement Therapy.
Soung Seol Kim
J Korean Endocr Soc. 1997;12(2):139-142.   Published online January 1, 2001
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No abstract available.
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Influence of Occupational Exposure on Gonadal Function.
Ki Hyun Park
J Korean Endocr Soc. 1997;12(2):143-154.   Published online January 1, 2001
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No abstract available.
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Clinical Features of Pityitary Hyperplasia.
Kyoung Rae Kim, Sung Kil Lim, Young Jun Won, Seok Ho Kwon, Bong Soo Cha, Young Duk Song, Hyun Chul Lee, Kap Bum Huh, Bo Young Choung, Su Yeun Nam, Sun Ho Kim, Tse Sung Kim, Jae Hwa Um
J Korean Endocr Soc. 1997;12(2):155-164.   Published online January 1, 2001
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BACKGROUND
S: Pituitary hyperplasia can mimic pituitary adenoma. In MRI, enlarged pituitary gland is enhanced homogenously with upward convexity of the superior margin of the gland .The best definition of hyperplasia in the pituitary hyperplasia seems to be a multiplication of one or more cell types. But definition, etiology and clinical courses of this disease are not clear, METHOD: We reviewed clinical symptoms, MRI, and pathologic findindings in 6 patients with pituitary hyperplasia. RESULT: 1. Major clinical symptoms were headache (100%), visual field defect (84%), polyuria/polydipsia (64%), and irregular mensturation (32%). Other symptoms were amenorrhea (16%) and galactorrhea (16%). 2. Three of five cases showed abnormal responses to combined pituitary function test, 3. MRI findings were pituitary hyperplasia (4), macroadenoma (l), and microadenoma (1). 4. In two operated cases, there was no adenoma. One case showed hyperplasia of lactotroph cells, the other was hyperplasia of gonadotroph cells confirmed by the examination of immunocytochemistry. CONCLUSION: Pituitary hyperplasia should be considered in patients with enlarged pituitary gland without focal mass lesion.
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Piruitray Thyrotropin-Secreting Tumors in Korean.
Chul Hee Kim, Ghi Su Kim, Hong Kyu Kim, Joong Yeol Park, Young Kee Shong, Sang Bum Hong, Jung Min Ko, Chang Jin Kim
J Korean Endocr Soc. 1997;12(2):165-175.   Published online January 1, 2001
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BACKGROUND
Thyrotropin-secreting pituitary adenoma is an uncommon disease and about 150 cases has been reported in the world literature. In Korea, only seven cases were reported as yet. The authors recently experienced four cases of TSH secreting pituitary tumor and analyzed the clinical characteristics and treatment outcomes of TSH-secreting tumors in Korean. METHODS: We analyzed clinical records of the four cases who had been recently treated at Asan Medical Center and the Korean literature which deals with the previously reported seven cases of TSH-secreting pituitary tumor. RESULTS: The average age at diagnosis was 37 years (ranging from 11 to 55 years). Four were men and seven were women. After the detection of hyperthyroidism, TSH-secreting pituitary adenoma was diagnosed 3.6 years later on the average. Ten patients presented with hyperthyroidism, but one had primary hypothyroidism. Typical features of acromegaly were observed in two patients. Visual disturbance was present in three cases, and galactorrhea was present in one case. Serum TSH concentrations ranged from 1.5 to 42.5uIU/mL showing mildly elevated or unsup-pressed TSH levels despite of elevated serum thyroid hormone concentrations. Among six cases in whom a-subunit level was measured, five showed elevated a-subunit level and a-subunit/TSH molar ratio. Two of 11 cases had microadenoma and the remainder had macroadeno#ma. Immunohisto-cheical studies were done in eight cases and revealed that three were positive for TSH only and five patients were positive for multiple hormones. Eight patients underwent transsphenoidal pituitary surgery and seven (88%) of them were cured. External irradiation or octreotide was used as adjunctive treatment in three cases. After treatment, TSH levels decreased in all six patients studied, hyperthyroidism was eliminated in all eight patients studied and visual disturbance was improved in two patients. CONCLUSION: Clinical characteristics of TSH-secreting pituitary adenoma in Koreans were similar with world literature, but were more common in women, had less visual disturbance and better surgical results. Diagnosis was commonly delayed for several years. TSH-secreting pituitary adenoma may be diagnosed more frequently and earlier with widespread use of sensitive TSH assay and early and proper diagnosis would lead proper treatments with improved outcome.
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Heterogeneity of TSH Receptor Autoantibodies in Autoimmune Thyroid Disease.
Won Bae Kim, Bo Youn Cho, Kyoung Ah Kim, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
J Korean Endocr Soc. 1997;12(2):176-193.   Published online January 1, 2001
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BACKGROUND
It has been known that most of thyroid stimulating antibodies (TSAbs) may interact with epitopes near N-terminal, and thyroid stimulation blocking antibodies (TSBAbs) near C-terminal on the extracellular domain of TSH receptor. However, many authors have reported different results about epitopes reacting with TSH receptor autoantibody (TRAb). TSBAbs inhibit thyroid stimulation of TSH and TSAbs at the receptor level. However, it has been reported that there are some TSBAbs which bind to the other sites, not TSH receptor, or block post-reeeptor process. These findings raise the possibility that TRAbs may be heterogeneous according to the mechanism of action. In order to investigate the heterogeneity of TRAb, we undertook immuno-precipitation using synthetic peptides of TSH receptor and measured TRAb activities by FRTL-5 cells and chimeric CHO cells. METHODS: We studied 102 patients with autoimmune thyroid disease (Graves disease 32, Hashimotos thyroiditis 29, atrophic thyroiditis 41) and 35 healthy persons. Three synthetic peptide fragments of TSH receptor were used to perform immunoprecipitation with serum or IgG of patients and healthy persons, TSAb and TSBAb activities were measured by FRTL-5 cells and CHO cells transfected with wild-type and 2 mutant TSH receptor cDNA (Mc2, Mc1+2). Mc2 and Mcl+2 were rnade to substitute amino acid residues of 90-165, 8-165 of the TSH receptor with corresponding residues of LH/CG receptor, respectively. RESULTS: Two out of 10 IgGs extracted from Graves disease and 2 out of 9 IgGs from atrophic thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide I (amino acid residue 35-50). Four out of 18 IgGs from Graves disease, 9 out of 41 IgGs from atrophic thyroiditis, and 6 out of 14 IgGs from Hashimotos thyroiditis had specific bidings over 0.84% in immunoprecipitation with peptide II (amino acid residue 317-332). Only 2 out of 10 IgGs from Graves disease had specific bidings over 0.84% in immunoprecipitation with peptide III (amino acid residue 341-358). When 10 IgGs extracted from Graves disease were reacted with wild-type, Mc2, and Mcl+2 CHO cells, 7 IgGs in wild-type and 4 IgGs in Mc2 had positive for TSAb activities. In 10 IgGs from atrophic thyroiditis, 5 in wild-type, 5 in Mc2, and 3 in Mcl+2 CHO cells had positive for TSBAb activities. In Hashimoto's thyroiditis, only 1 with hyperthyroidism had positive for TSAb activity in wild-type and 1 with hypothyroidism had positive for TSBAb activities in both of wild-type and Mc2 CHO cells. Therefore, patients with Graves disease were divided into at least 3 groups according to the TSAb activities measured by wild-type, Mc2, Mcl+ 2 CHO cells and TBII activities. And patients with atrophic thyroiditis were divided into at least 4 groups according to the TBII activities, TSBAb activities by wild-type, Mc2, Mcl+2 CHO cells and FRTL-5 cells. CONCLUSION: From these results, epitopes of TSH receptor reacting with TSAb or TSBAb in autoimmune thyroid disease may be scattered in the TSH receptor, although epitopes of TSAb tend to be near N-terminal and those of TSBAb near C-terminal. Graves disease or atrophic thyroiditis were divided into 3 or 4 groups according to the TBII and TRAb activities. Therefore, TRAb detected in autoimmune thyroid disease may be heterogenous.
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Changes in Properties of Thyrotropin Receptor Antibodies Following Radioiodine Treatment in Patients with Graves' Disease.
Won Bae Kim, Hyun Kyung Chung, Bo Youn Cho, Hong Kyu Lee, Chang Soon Koh, Do Joon Park, Yeon Sahng Oh
J Korean Endocr Soc. 1997;12(2):194-206.   Published online January 1, 2001
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BACKGROUND
It has been suggested that thyroid stimulation blocking antibody (TSBAb) is involved in the development of early hypothyroidism after radioiodine treatment in patient with Graves disease. However, previous studies have reported the effect of radioiodine treatment on overall changes of TSH receptor antibodies without detailed observation of changes in properties of TSH receptor antibodies. The aim of this study is to evaluate the effect of radioiodine treatment on thyroid stimulation antibody (TSAb) or on thyroid stimulation blocking antibody (TSBAb) activities and to see whether the appearance of TSBAb after radioiodine treatment is involved in the development of early hypothyroidism in patients with Graves disease. METHODS: The activities of TSAb, TSBAb were measured serially with human TSH receptor transfected Chinese hamster ovary (CHO) cells in 36 patients with Graves disease who received 131I treatment. In addition to the wild type TSH receptor-expressing cells, we used a chimeric receptor that 90-165 amino acid residues were substituted by those of rat LH/CG receptor (Mc2) for measurement of TSBAb without interference by the presence of TSAb and for evaluation of TSAb epitope spreading. We evaluated the association of early hypothyroidism after 131I treatment with changes of various immunologic parameters. RESULTS: In 14 (39%) of 36 patients, TSBAb activities were present in their sera before or after 131I treatment. Four of them had TSBAb activities before 131 treatment, and 12 newly acquired TSBAb activities after 131I treatment. The existence of TSBAb was not associated with the development of early hypothyroidism after 131I treatment but with low TSAb activities before 131 treatment, high thyroidal uptake of 131I given and with old age. The phenomena of epitope spreading measured by TSAb with Mc2 mutant clone before and after 131I treatment was not infrequent, but it had no clinical relevance. CONCLUSION: These results suggest that the existence of TSBAb may be not a major factor in the development of early hypothyroidism after radioiodine treatment in Graves disease. Other factors such as TSAb activities before radioiodine treatment, the efficiency of thyroidal uptake of 131I or old age are associated with the development of early hypothyroidism.
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Non-association of Pvull and Xval Estrogen receptor Genotypes with Bone Mineral Density and Bone Markers in Korean Premenopausal Women.
Hyun Koo Yoon, Ho Yeon Chung, In Gul Moon, Chang Hoon Yim, Sang Woo Kim, Ki Ok Han, In Kwon Han, Hun Ki Min, Dong Won Suh, Dong Hee Cho, Bo Kyung Park, Jong Tae Choi
J Korean Endocr Soc. 1997;12(2):207-214.   Published online January 1, 2001
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BACKGROUND
Bone mineral density (BMD) is under strong genetic control. A recently reported case of severe estrogen resistance caused by a germ-line mutation at the estrogen receptor gene locus suggests the possibility that other variants of the estrogen receptor (ER) gene could be responsible for the heritable components of bone density. METHODS: Two restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as PvuII and XbaI, and their relationship to bone mineral density (BMD) and bone turnover markers were examined in 95 healthy premenopausal women. Their mean age was 29 +-6.9 years (mean+-SD). RESULTS: The distribution of the PvuII and XbaI RFLPs was as follows: PP 20 (21.1%), Pp 40 (42.1%), pp 35 (36.8%), and XX 5 (5.3%), Xx 33 (34.7%), xx 57 (60.0%) (capital letters signify the absence of, and lower case letters signify the presence of the restriction site of each RFLP). There was no significant relation between ER genotypes and BMD measured at several sites such as lumbar spine (L2-4), distal forearm, and femoral neck. Also no significant genotypic differences were found in the several biochemical markers and sex hormone status. CONCLUSION: These data indicate that these polymorphisms are not predietive of bone turnover nor BMD in a sample of healthy Korean premenopausal women.
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Changes of Bone Mineral Density and Levels of Cytokines in the Culture Media of Bone Marrow Monocytes after Ovariectomy in Rats.
Keun Yong Park
J Korean Endocr Soc. 1997;12(2):215-221.   Published online January 1, 2001
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BACKGROUND
Although the mechanism of the increase in bone resorption induced by estrogen deficiency is still controversial, recent studies have suggested that estrogen may modulate the secretion of bone resorption cytokines that are produced in the bone microenvironment and influence bone remodeling. Among them, IL-1 and TNF-a promote bone resorption by stimulating the activity of mature osteoclasts and the differentiation of osteoclast precursors and the production of these cytokines are mediated by estrogen. We performed this study to evaluate the effect of ovariectomy on bone mineral density and levels of cytokines in the culture media of bone marrow monocytes. METHODS: The experimental animals were 23 female Sprague-Dawley rats that were 8 weeks of age and weighed an average of 176.8 gm at the beginning of the study. Bilateral ovariectomy (n=13) and sham-operation (n=10) were performed in all rats from a ventral approach. Bone mineral density (BMD) of the total body and levels of IL-1 and TNF-a of culture media of bone marrow monocytes were measured before and 8 weeks after operation with using DPX-L and ELISA assay, respectively. Serum levels of LH, FSH, E2 were measured by RIA assay. RESULTS: BMD of total body was lower after ovriectomy (0.24+-0.04g/cm) than before ovariectomy (0.27+-0.03g/cm), but there was no statistically significant difference in sham-operation group. Serum levels of LH, FSH were higher after ovariectorny (0.87+-0.36 mIU/mL, 9.47+-1.26 mIU/mL) than before ovariectomy (0.10+-0.06mIU/mL, 2.09+-0.41mIU/mL) (p<0.01) and serum level of E was lower after ovariectomy (10.98+-8.71pg/mL) than before ovariectomy (7350.77+-417.29 pg/mL) (p<0.01), respectively. Levels of IL-1 and TNF-a in culture media of bone marrow monocytes were higher after ovariectomy (23.48+-3.98pg/mL, 52.64+-5.31 pg/mL) than before ovariectomy (9.72+0.94pg/mL, 24.37+-3.39pg/mL) (p<0.01), but there were no statistically significant differences in the sharn-operation group. CONCLUSION: It is possible that increased production of IL-1 and TNF-a in estrogen deficiency induced by ovariectomy occures in the bone microenvironment and these cytokines may play a critical causal role in inducing bone loss.
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The Role of Low-dose ACTH Stimulation Test in the Diagnosis of Adrenal Insufficiency.
Chul Hee Kim, Ghi Su Kim, Hong Kyu Kim, Joong Yeol Park, Young Kee Shong, Ki Up Lee, Il Min Ahn, Sung Kwan Hong
J Korean Endocr Soc. 1997;12(2):222-229.   Published online January 1, 2001
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BACKGROUND
Rapid adrenocorticotropin (ACTH) stimulation test using 250ug of ACTH (1-24) has been used as a standard test in the initial assessment of adrenal function. However, it has recently been suggested that a rnaximal cortisol response can be achieved with a much lower ACTH dose, and reducing the dose might further enhance the sensitivity of the test in the detection of mild adrenal insufficiency. This study was performed to evaluate the role of low-dose (lug) ACTH stimulation test in the assessment of adrenal function and the diagnosis of subtle adrenal insufficiency. METHODS: Twenty-two subjects with suspected adrenal insufficiency due to long-term corticosteroid use were included in this study. The correlations between clinical features and the serum cortisol responses to low dose (lug) and high dose (250 ug) ACTH stimulation were evaluated. RESULTS: In high dose test, 10 (67%) out of 15 subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response (peak cortisol level <18 ug/dL), but 5 (33%) subjects showed normal response (peak cortisol level > 18ug/dL). On the other hand, 14 (93%) subjects with clinical features of adrenal insufficiency showed decreased serum cortisol response in low dose test, while only one showed normal response. In 7 subjects without clinical features of adrenal insufficiency, 5 subject (71%) showed normal response, and 2 subjects (29%) showed decreased response in both low and high dose tests. CONCLUSION: These results suggest that the 1-ug low dose ACTH stimulation test might be more sensitive than conventional 250-ug test in the detection of mild adrenal insufficiency. Further studies are needed to determine the optimal dose of ACTH and the criteria for normal response to ACTH stimulation.
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Mechanism of Angiotensin 2-Stimulated Aldosterone Secretion in Adrenal Glomerulosa Cells of Diabetic Rats ; Normal Phospholipase Activity and Intracellular Calcium Mobilization.
Yeon Ah Sung, Nan Ho Kyung
J Korean Endocr Soc. 1997;12(2):230-244.   Published online January 1, 2001
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BACKGROUND
Diabetic patients develop hypoaldosteronism which frequently caused hyperkalemia and metabolic acidosis and diabetic hypoaldosteronism is associated with selective unresponsiveness of aldosterone to angiotensin A-II, but mechanism of defect in A-II stimulated aldosterone response still remain unclear. METHODS: To elucidate the mechanism of defect in A-II stimulated aldosterone response, author evaluated the responses of aldosterone production to A-II, K+, and ACTH in adrenal glomerulosa cells prepared from streptozotocin induced diabetic rats, Inositol triphosphate (IP3) generated by activation of phospholipase C (PLC) and arachidonic acid and lysophospholipids generated by activation of phospholipase A2 (PLA2) were measured in A-II stimulated glomerulosa cells. Radiocalcium efflux and aldosterone response to second messenger of A-II such as PLC, IP3, PLA, AA and protein kinase C activator, 12-o-tetradecanoylphorbol 13 acetate (TPA). RESULTS: 1. Plasma renin activity and aldosterone levels were not different among control rats, untreated and insulin treated diabetic rats. 2. Basal, ACTH and K+ -stimulated aldosterone production were similar in cells from the three groups (p<0.05), but A-II stimulated aldosterone production was significantly decreased in cells from untreated diabetic rats compared with control and insulin treated diabetic rats (p0.05). 4. Aldosterone responses to PLC, IP3, AA and TPA were significantly decreased in glomerulosa cells from diabetic rats compared with control and insulin treated diabetic rats (p<0.05), but aldosterone response to PLA2 was similar among the three groups (p>0.05). 45Ca efflux to PLC, IP3 PLA2 and AA were similar among the three groups (p>0.05). CONCLUSION: These results suggested that decreased A-II-stimulated aldosterone response was present in glomerulosa cells from streptozotocin induced diabetic rats and reversed by insulin treatments. The main defect of altered A-II response of zona glomerulosa might be located in the step after activation of phospholipase and increase of intracellular calcium, and activation of PKC, or distal to that could be one of the causative mechanism.
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Changes in Plasma Dehydroepiandrosterone-Sulfate ( DHEA-S ) Level & DHEA-S / cortisol Ratio by Age in Healthy Korean.
Jae Myung Yu, Cheol Soo Park, Hyung Joon Yoo, Kwon Yeop Lee, Kyu Yong Park, Cheol Hong Kim, Min Sook Park, Hyun Gyu Kim, Du Man Kim, Sung Hee Ihm, Moon Gi Choi, Sung Woo Park
J Korean Endocr Soc. 1997;12(2):245-154.   Published online January 1, 2001
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BACKGROUND
DHEA-S is the most abundant steroid hormone in circulation, and primarily secreted from the adrenal cortex, but its physiological role is little known. One of the characteristic features of DHEA-S is progressive decrement of plasma DHEA-S level with advancing age, in contrast, plasma levels of other adrenal hormones are not chaging or littie decreasing. To grasp the trends of plasma DHEA-S level and DHEA-S/cortisol ratio by age in healthy Korean, we measured the plasma DHEA-S levels and DHEA-S/cortisol ratios in healthy Korean. METHODS: Healthy Korean (men: 99, women: 102, age range: 15-97 year old)were studied. Subjects were not taking drugs (such as glucocorticoid or androgenic medication) or cigarettes known to modify the plasma level of DHEA-S and cortisol, and had no evidence of hepatic, renal disease or hyperlipidemia as determined by serum lipid, bilirubin, SGOT, SGPT, BUN, creatinine. Data were analyzed by 10-year age group for men and women: i.e, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89 and 90 year or more. Plasma DHEA-S levels were measured by using a commercially available RIA kit with 125I labeled-DHEA-SO4 (Coat-A Count DHEA-SO4), and for the measurement of plasma cortisol levels, commercial Gamma Coat TM[125I] Cortisol Radioimmunassay Kit was used. RESULTS:. 1) In both men and women, plasma DHEA-S level showed high interindividual variation within the same age group. 2) There were individual sex differences in plasma levels of DHEA-S, in all age groups, plasma DHEA-S levels were significantly higher values for men than for women. 3) Maximum plasma DHEA-S levels (men; 237+-3.35 ug/dL, women; 108+-17.5 ug/dL) were at third decade in both men and women. 4) Both men and women showed the continuous decline in plasma DHEA-S level with age. These age-related decline was more prominent in men than in women (men; y=-3.152 * +292.6, r2= 0.8459, P<0.05, women; y= -1.417 * +143.3, r2 = 0.7278, P< 0.05). 5) As an index of aging, there was no stastical difference between DHEA-S and DHEA-S/cortisol ratio. CONCLUSION: In healthy Korean, there were high interindividual variation of plasrna DHEA-S levels. In both men and women plasma DHEA-S level was peak at third decade, and from when it declined progressively with age. These results suggest that although the reliability of single plasma DHEA-S measurement are limited, the decline of DHEA-S with advancing age might be a specific marker of endocrinologic hormonal milieu (aging index). Also, concerning to individual adrenal secreting capacity, we measured DHEA-S/cortisol ratio. But we did not found that plasma DHEA-S/cortisol ratio is superior to the plasma DHEA-S level as an aging index.
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2-Bromopropane as a New Etiology of Primary Ovarian Failure.
Chul Hee Kim, Ghi Su Kim, Jung Min Ko, Eun Sug Sin, Hyo Jung Kim, Young Tak Kim, Kyoung Sik Cho, Ghil Suk Yoon
J Korean Endocr Soc. 1997;12(2):255-264.   Published online January 1, 2001
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BACKGROUND
Primary ovarian failure is reportedly increasing in recent years. Environmental factors have been frequently implicated as responsible for this increase, However, only a few of the environmental factors have been proven to cause the ovarian failure in human. METHODS: In June 1995, 24 female laborers, who worked in a factory which used Solvent #5200 (with a main chemical component being 2-bromopropane), developed symptoms of amenorrhea or irregular menstruation. All subjects underwent laboratory tests including measurement of serum LH, FSH, and estradioL Magnetic resonance imaging and ultrasonography of the pelvis were performed in all subjects. Laparoscopic examination was performed in 6 out of 24 patients after obtaining informed consent and 4 of 6 underwent ovarian biopsy. RESULTS: One subject was excluded because she had undergone hysterectomy previously. Among the remaining 23 subjects, 14 and 9 complained of amenorrhea and irregular menstrual periods, respectively. When we defined primary ovarian failure as FSH>30mIU/mL, all of those 14 patients with amenorrhea could be classified as primary ovarian failure. On the other hand, those 9 patients with irregular menstruations had normal FSH levels. Pathologic examination of ovaries showed interstitial fibrosis, loss of primordial follicles, and development arrest of follicles in the group with amenorrhea, similar to what is found in those who received chemotherapy or were exposed to radiation. CONCLUSION: The female laborers who were exposed to the solvent with 2-bromopropane developed primary ovarian failure. This failure was associated with longer duration of exposure. To our knowledge, this is the first report in the world indicating 2-bromopropane as a possible agent for ovarian failure.
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Effects of Superoxide Dismutase on Changes in EDRF-and EDHF-Mediated Relaxation of Diabetic Rat Aortas Exposed to Oxygen Free Radicals.
Dong Hee Kim, Ye Kyung Seo, Jik Hwa Nam, Byung Ho Sin, Jung Guk Kim, Sung Woo Ha, Bo Whn Kim
J Korean Endocr Soc. 1997;12(2):265-274.   Published online January 1, 2001
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BACKGROUND
The relaxative response of blood vessels to acetylcholine (ACh) is known to be abnormal in diabetic rat due to changes in endothelium-derived relaxing factor (EDRF) and/or endothelium-derived hyperpolarizing factor (EDHF)-mediated action. Oxygen free radical (OFR) interferes with endothelium dependent relaxation to ACh in diabetic rats; this effect rnay be prevented by superoxide dismutase (SOD), OFR scavenger. Then, we determined the effect of SOD on modulation of OFR-induced damage to EDRF and EDHF-mediated relaxations to ACh in diabetic rat aortas. METHODS: After aortas were incubated with free radical generating system for 15 min with or without SOD pretreatment (150 U/mL) and contracted submaximally by norepinephrine (10 (-5) M), relaxative responses to cumulative concentrations (10 (-9) M to 10 (-5) M) of ACh were measured in aortas isolated from the control and 6-8 week streptozotocin-induced diabetic rat. We measured relaxative responses to ACh in these aortas treated with calmidazolium (100uM) or N-nitro-L-arginine methyl ester (luM) after exposure to OFR with/without SOD pretreatment, RESULTS: The ACh-induced relaxation (10 (-9)M to 10 (-5) M) was significantly decreased in diabetic than in control rat aortas (p<0.05). ACh-induced relaxation in diabetic rat aortas was significantly impaired from 79.3% to 71.2% after exposure to OFR (p<0.05), and the degree of ACh-induced relaxation was recovered from 71.2% to 84.0% after pretreatment with SOD (p<0.05). EDRF-mediated relaxation to ACh in diabetic rat aortas was significantly impaired from 71.2% to 61.6% after exposure to OFR (p<0.05), and the degree of impairment of ACh-induced EDRF-mediated relaxation was recovered from 61.6% to 76.0% after pretreatment with SOD. After exposure to OFR, EDHF-mediated relaxation to ACh in diabetic rat aortas was not significanlty impaired. However, the degree of impairment of EDHF-mediated relaxation to ACh was recovered from 46.0% to 59.5% after pretreatment with SOD. CONCLUSION: This study suggests that OFR may impair mainly EDRF-mediated relaxation to ACh and SOD may protect rnainly OFR-induced damage to EDRF-mediated relaxation to ACh in diabetic rat aortas.
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Glucose metabolism in chronic hepatitis B infection-acute insulin response and glucose disappearance rate to intravenous glucose.
Chan Soo Shin, Kyoung Soo Park, Seong Yeon Kim, Hong Kyu Lee, Chang Soon Koh, Young Bae Kim
J Korean Endocr Soc. 1997;12(2):275-282.   Published online January 1, 2001
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BACKGROUND
Glucose intolerance and diabetes mellitus are frequently observed in chronic liver disease. However, the causal relationships between these two are difficult to prove. Chronic hepatitis B infection, which is prevalent in Korea, is thought to be a good model to study the natural history of abnormal glucose metabolism in chronic liver disease because many patients with chronic hepatitis B infection eventually progress to liver cirrhosis. METHODS: In order to evaluate glucose metabolism in chronic hepatitis B infection, we did intravenous glucose tolerance test in patients with chronic hepatitis B and age, sex and body mass index matched controls and compared the first phase insulin response and glucose disappearance rates between 2 groups. RESULTS: Patients with chronic hepatitis B showed lower glucose disappearance rate and higher plasma insulin and C-peptide area (0-10min after iv glucose) than controls. Patients with decreased glucose disappearance rate had higher AST level and decreased plasma C-peptide area (0-10min). CONCLUSION: Most of the patients with chronic hepatits B infection is associated with insulin resistance and compensatory increase in the first phase insulin secretion. Inadequate insulin secretion may contribute to decreased glucose disappearance rate in these patients.
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Expression of Phospholipase C-B3 using Recombinant Baculovirus Expression System.
Do Joon Park
J Korean Endocr Soc. 1997;12(2):283-294.   Published online January 1, 2001
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BACKGROUND
Although phospholipase C (PLC)-B3 is thought to be a very important enzyme in intracellular signal transduction, the sophisticated and complicated purification steps make it difficult to obtain sufficient amount of protein to study regulation of its activity by G proteins or other proteins. In order to get large amount of PLC-B3 protein, I employed baculovirus expression system which is known to express large amount of functionally active proteins. METHODS: In order to make recombinant baculovirus which expresses PLC-B3 gene, partial cDNA of PLC-B3 which lacked 51 nucleotides was used to make full length PLC-B3 cDNA. By PCR, 5-end sequence of PLC-B3 was ligated into partial rat PLC-B3 cDNA and later cloned into pVL1393 transfer vector to make recombinant baculovirus. This recombinant baculovirus containing PLC-B3 sequence was used to infect Sf9 insect cells. RESULTS: Infection of Sf9 cells with recombinant baculovirus rendered expression of 152 kDa-PLC-B3 protein, which was confirmed by immunoblot assay and PLC activity assay. CONCLUSION: The whole length PLC-B3 cDNA was expressed in Sf9 cells using baculovirus expression system. By using it, homogeneous enzyme is expected to be purified to study precise activation and regulation mechanisms of PLC-B3.
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Endocrinol Metab : Endocrinology and Metabolism