- Gene Expression of the Somatostatin Receptors, Gi2 alpha and Pit-1 alpha in GH3 Cells Permanently Transfected with a Mutant Gs alpha Gene.
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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
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J Korean Endocr Soc. 2002;17(2):170-182. Published online April 1, 2002
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- 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.
- Gene Expression of Somatostatin Receptor (Subtype 2 & 5), Gi2 alpha and Pit-1 in GH-secreting Pituitary Adenomas.
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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
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J Korean Endocr Soc. 2002;17(2):158-169. Published online April 1, 2002
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- 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.
- The Significance of Plasma ADH in Differential Diagnosis of Central Diabetes Insipidus.
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Ho Jong Lee, In Myung Yang, Sun Kee Min, Jung Hyun Noh, Cheol Young Park, Seung Joon Oh, Deog Yoon Kim, Jung Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 2001;16(4-5):438-446. Published online October 1, 2001
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- BACKGROUND
Although the water restriction test(WRT) has been used as a standard test for the differential diagnosis of diabetes insipidus(DI), the measurement of plasma ADH concentration is also known to be useful method for differential diagnosis. Recent studies have shown that some patients with idiopathic central DI(CDI) were found to have a lesion on follow-up imaging studies. There have been no report in Korea on plasma ADH measurement for the differential diagnosis of DI, nor on follow-up imaging study of the idiopathic CDI. METHODS: We retrospectively reviewed the clinical and laboratory findings of 26 patients(12 men, 14 women, age 9-65 years) with CDI, including pituitary MRI or CT scan, who had been diagnosed with WRT and had undergone plasma ADH concentration measurement. RESULTS: 1) Clinical features of the patients with complete CDI did not differ from those of patients with partial CDI. 2) Maximal urine osmolality of complete CDI and partial CDI were 168+/-69mOsm/kg and 431+/-141mOsm/kg, respectively, and the percentage increase in the urinary osmolality after ADH injection was 209+/-149% and 29+/-17%, respectively. 3) Among the 26 patients, 10 patients had their plasma ADH measured. Nine patients in this group were diagnosed as CDI by WRT and plasma ADH concentration of the 9 was compatible for CDI. The plasma ADH level was also inappropriately low in one patient who had been diagnosed with primary polydipsia by WRT, the patient was diagnosed as partial CDI. 4) The findings of follow-up MRI revealed isolated thickening of the pituitary stalk in two cases of idiopathic CDI diagnosed initially with MRI. CONCLUSION: This study suggests that the measurement of plasma ADH can ensure a better differential diagnosis between partial CDI and primary polydipsia, and that the patients with idiopathic CDI should be examined regularly with MRI brain scan, including the pituitary gland.
- The Combined Pituitary Stimulation Test in Patients Suffered from Massive Postpartum Hemorrhage.
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Sang Hwa Kim, In Myung Yang, Cheol Young Park, Seung Joon Oh, Deog Yoon Kim, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Sun Woo Kim, Young Kil Choi
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J Korean Endocr Soc. 2001;16(1):39-53. Published online February 1, 2001
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- BACKGROUND
ackground: Sheehan's syndrome secondary to severe postpartum hemorrhage is one of the major causes of pituitary insufficiency in Korea. Most of these patients do not manifest symptoms or signs of gross endocrinopathies. Earlier detection of pituitary insufficiency is of clinical importance. The combined pituitary stimulation test that uses the four hypothalamic releasing hormones is a rapid, safe, and effective way to evaluate anterior pituitary function. However, the criteria for a normal response has not been established in Korea. METHODS: Combined anterior pituitary stimulation tests were performed on fourteen healthy women who had no history of endocrine disease. Combined tests of anterior pituitary reserve were done no forty-five patients who suffered from massive postpartum hemorrhage which required transfusing, along with subsequent shock or changing consciousness and in thirty-nine patients who experienced mild postpartum hemorrhage. RESULTS: 1) In the severe hemorrhage group, thirty-three of forty-five women (73.3%) showed blunted responses in more than one of the anterior pituitary hormones in the combined pituitary stimulation tests. However, in the mild hemorrhage group, only eighteen of thirty-nine women (46.2%) demonstrated blunted responses of more than one of the anterior pituitary hormones. 2) In the severe hemorrhage group, the TSH response was blunted in twenty-five patients (55.6%), prolactin in eleven patients (24.4%), ACTH in ten patients (22.2%), LH in ten patients (22.2%), GH in nine patients (20%), and FSH in five patients (11.1%). 3) The results of combined pituitary stimulation tests in the normal control group were different from the results of other studies. CONCLUSION: It is recommended that the women who experienced a severe postpartum hemorrhage should be evaluated by using the combined pituitary stimulation test. Moreover, criteria for a normal response to the combined pituitary stimulation test should be established in Korea.
- Effect of Acute Hyperglycemia - and Isoproterenol - induced Hypothalamic Somatostatin Release on the Thyroid Hormone Releasing Hormone - induced Thyroid Stimulating Hormone Secretion.
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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
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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.
- Thyrotropin-releasing Hormone(TRH) Receptor Gene Expression in GH3 Cells Permanently Transfected with a Mutant Gs alpha Gene.
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Seung Joon Park, In Myung Yang, Sung Vin Yim, Joo Ho Chung, Jee Chang Jung, Kye Chang Ko, Young Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 2000;15(1):46-54. Published online January 1, 2001
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Gs alpha gene mutation, that constitutively increases intracellular cAMP, is found in some acromegalic patients. It was demonstrated that increased intracellular cAMP levels suppress the expression of rat TRH receptor (TRH-R) mRNA. We previously demonstrated that transient expression of a mutant Gs alpha gene suppress the rat TRH-R gene expression in the cultured rat growth hormone-secreting tumor cell line (GH3), whereas TRH-R gene expression in adenomas with Gs alpha gene mutation (gsp oncogene) did not differ from that in tumors without the mutation. The discrepancy suggests the possibilities that the effect of permanent expression of mutant Gs alpha gene on TRH-R gene expression is different from that of transient expression of the mutant gene and hypothalamic hormones including TRH regulate the gene expression. METHODS: We investigated whether permanent expression of the mutant-type Gs alpha does not suppress the TRH receptor gene expression in GH3 cells, and whether TRH suppresses the gene expression by using reverse transcription-polymerase chain reaction (RT-PCR) and in vitro transcription. RESULTS: Permanent expression of a mutant-type Gs alpha increased basal cAMP levels up to 1.7-fold relative to the controls, whereas the wild-type cell line did not show increased cAMP levels. Permanent expression of a mutant-type Gs alpha increased TRH receptor mRNA level up to 2.8 fold compared with the controls. Treatment of the permanently transfected GH3 cells with TRH suppressed TRH-R gene expression more prominently compared to the wild type GH3 cells. CONCLUSION: These results suggest that permanent expression of mutant Gs alpha enhances the expression of TRH-R in GH-secreting pituitary tumors with gsp oncogene, but the gene expression may also be regulated by other factors including TRH.
- The Effect of Slow Release Lanreotide in Korean Acromegalic Ratients.
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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
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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.
- Cytotoxic T Lymphocyte Antigen-4 (CTla-4) Polymorphism in Korean Autoimmune Thyroid Disease.
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Dong Kuen Lee, Young Seol Kim, Jeong Taek Woo, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Kil Choi, Jeong Ryung Paeng
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J Korean Endocr Soc. 1999;14(1):40-52. Published online January 1, 2001
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- BACKGROUND
The cause of autoimmune thyroid diseases (AITD), including Graves disease and Hashimotos thyroiditis, is largely unknown. To identify the genes responsible, most attention has been focussed on the HLA regions in the early studies. However, these studies have repeatedly shown a weak association between AITD and the HLA-DR3 in Caucasians. To understand and find out the mechanisms underlying the development of AITD, a search for non-HLA linked susceptibility genes is important. A recent study from American population have indicated an association between a polymorphism of CILA-4 gene and Graves disease. To clarify the relationship of the CTLA-4 polymorphism and AITD, the allele frequency of CTLA-4 gene from the patients with Graves disease and with Hashimotos thyroiditis in Korean papulation were analysed. METHODS: The CTLA-4 exon 1 polymorphism (49, A/G) was analysed by PCR-based, RFLP (Restriction Fragment Length Polymorphism) from 92 women and 37 men with Graves disease and 50 women and 9 men with Hashimotos thyroiditis diagnosed. Also, 287 healthy controls including 155 women and 132 men with no clinical evidence or family history of thyroid disease were enrolled. RESULTS: 1) In the group of Graves disease, there was significantly more patients with alanine homozygote (GG) than in control group (P<0.0005, RR=1.40). However, there was not significant with threonine homozygote (AA) between two groups (P=0.052). In the group of Hashimotos thyroiditis, no significant differences were found between all homozygotes and heterozygote. 2) In the group of Graves disease, there were significantly more patients with alanine homozygote (GG) (P<0.0001, RR=1.85) and significantly fewer patients with threonine homozygote (AA) than in the group of Hashimoto's thyroiditis (P<0.005, RR 0.25). CONCLUSION: Regardless of sex difference, alanine homozygote (GG) at exon 1 (codon 17) of CTLA-4 is associated with Graves disease in Korean population, which suggests genetic susceptibility is some role in the pathogenesis of Graves disease.
- Effect of Ga2 gene mutation on the Expression of Thyrotropin-Releasing Hormone ( TRH ) Receptor Gene in GH3 Cells.
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Seung Joon Park, In Myung Yang, Jeong Hwa Ryu, Joo Ho Chung, Jee Chang Jung, Kye Chang Ko, Young Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 1997;12(3):357-363. Published online January 1, 2001
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- Expression of TRH Receptor Gene in GH-Secreting Piruitary Adenomas.
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In Myung Yang, Seung Joon Park, Jeong Wha Ryu, Joo Ho Chung, Mee Sook Ryu, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 1997;12(3):349-356. Published online January 1, 2001
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- Background
To test the hypothesis that Galphas gene mutation may suppress the expression of TRH-R gene, we investigated whether hTRH-R gene expression is lower in human GH-secreting pituitary adenomas with Galphas mutation than in tumors without the mutation. Method: TRH-induced paradoxical response of GH was observed in 8 acromegalic patients. The mutation of gene was identified by direct sequencing of the genomic DNA prepared from GH-secreting pituitary adenomas. The expression of hTRHT mRNA was quantitated by RT-PCR. Results: The transcript of hTRH-R gene was detected in 6 of 8(75%) tumors. Three of these(50%) showed the paradoxical GH response to TRH and the other three patients did not show the response. The relative expression of hTRH-R mRNA in the tumors from patients with the paradoxical response of GH to TRH did not differ from that in the tumors from patients without the paradoxical response. Direct PCR sequencing of Galphas disclosed a mutant allele and a normal allele only at codon 201 in 4 of 8 tumors. The paradoxical response to TRH was observed in 2 of 4 patients without the mutation, and 2 of 4 patients with the mutation. The hTRH-R gene expression of pituitary adenomas did not differ between the tumors without the mutation and those with mutation. Conclusion: This study suggests that the expression of TRH-R gene is not likely to be a main determinant for the paradoxical response of GH to TRH, and that Galphas mutation does not seem to suppress the gene expression of TRH-R in GH secreting adenoma.
- A Case of Multiple endocrine neoplasia type 2a.
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Seung Jae Hong, In Myung Yang, Jeong Taek Woo, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Yong Sun Yun, Chung Hwan Lee, Seong Ho Lee, Deok Yoon Kim, Sung Weon Kim
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J Korean Endocr Soc. 1997;12(2):328-337. Published online January 1, 2001
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- Multiple endocrine neoplasia type2a (MEN type2a) is a dominantly inherited cancer syndrome which is characterized by medullary thyroid carcinoma, pheochromocytoma and parathyroid hyperplasia or adenoma. Recent reports show that DNA analysis will be introduced into screening of MEN type2a families. Regular prospective screening and appropriate surgical intervention can reduce the morbidity and mortality due to MEN type2a. We experienced a case of MEN type 2a in a 46-year-old female patient. She had undergone bilateral adrenalectomy due to pheochromocytoma, followed by a total radical thyroidectomy, which revealed medullary thyroid carcinoma of the both thyroid gland and parathyroid hyperplasia.
- A Study of Point Mutations of Human Insulin-like Growth Factor - 1 (IGF - 1) Promoter Gene in Familial Short Stature (FSS) Patients.
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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
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J Korean Endocr Soc. 1996;11(4):500-509. Published online November 7, 2019
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- 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.
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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
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J Korean Endocr Soc. 1996;11(4):479-491. Published online November 7, 2019
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- 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.
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Sung Woon Kim, Hyun Ha Chang, In Kyung Jung, Jeong Taek Woo, In Myung Yang, Jin Woo Kim, Soung Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 1996;11(4):409-417. Published online November 7, 2019
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- 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.
- Increased Somatostatinergic Activity Induced by Acute Hyperglycemia is Not Mediated by Stimulation of the Beta-adrenergic System.
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Seung Jae Hong, In Myung Yang, Gyu Choon Lee, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Soung Seol Kim, Young Kil Choi
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J Korean Endocr Soc. 1996;11(4):383-390. Published online November 7, 2019
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- Insulin Like Growth Factor-I and Insulin Like Growth Factor Binding Protein-3 in Human Thyroid Cystic Fluids.
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In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Byoung Joon Kim, Seung Joon Oh
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J Korean Endocr Soc. 1995;10(4):395-404. Published online November 7, 2019
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- In the thyroid tissue, thyrotrophin(TSH) and IGF-I played major role of the goitrogen. But the evidences and precise mechanism of these two factors were not known so much. Actually local secretion of thyroid IGF-I was originated from its fibroblasts mainly. We guessed major roles of IGFs in the thyroid tissue were local paracrine effect of thyroid cells proliferation and differentiation which concert with TSH. Recently, some reporters described the source of thyroid IGF-I were partly from thyroid follicular cells and its action were synergistic with TSH. We measured TSH, IGF-I and IGFBP-3 from sera and thyroid cystic fluids in 36 patients with simple thyroid cyst and examined into correlation between TSH, IGF-I and IGFBP-3.1) According to cyst/serum TSH ratio, we classified two groups(Group I; c/s TSH <1, n=19. Group II; c/s TSH >1, n=17). This classification criteria means that cystic TSH level were increased than that of serum or not.2) The serum TSH, IGF-I and IGFBP-3 levels are not difference between group I and II.3) Cystic TSH were dependent on the serum TSH in Group I, but negative correlation in Group II. In Group II, cystic TSH was significant increased.4) Serum IGF-I were positive correlation in each Group5) In Group II, cystic IGF-I was not exceed than those of serum IGF-I, but some cystic IGFBP-3 were more increased than those of serum.6) In Group II, cystic IGFBP-3 increased than serum TSH, and cystic IGFBP-3 was positive correlation with cystic TSH and cystic IGF-I.As these data suggested that cystic TSH and cystic IGF-I levels may influence cystic IGFBP-3 level. The main effect for maintenance of cyst was mediated by cystic TSH and cystic IGFBP-3. But the cystic IGFBP-3 has major role for thyroid cyst than cyst TSH.
- Identification of TPA - Response Element (TRE) in the Rat Thyrotropin - Releasing Hormone (TRH) Gene.
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Woon Won Jung, Young Kil Choi, In Myung Yang, Kwang Sik Seo, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Seung Joon Park
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J Korean Endocr Soc. 1994;10(3):200-213. Published online November 6, 2019
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- There are two potential imperfect copies of the TRE consensus sequence between -47 and -113bp position on 5' upstream of the rat TRH gene. The upstream element(5'-TGcCgTCA-3') is located between -101 bp and -94 bp, and the downstream element(5'-TGAcCTCA-3') is positioned between -59bp and -52bp relative to the stranscription start site. The downstream variant differs from the consensus sequence of TRE(AP-1)(5'-TGACTCA-3'), by addition of one nucleotide. As there is no direct evidence that TPA stimulates the transcription of rat TRH gene, and there is no study to define TRE of the rat TRH gene, we performed Northern blot assay, transient gene expression study and gel shift assay to identify TRE. TRH mRNA expression of CA77 cells was increased about 2-2.5 fold 30 min after TPA stimulation. When PC12 cells were stimulated by TPA after transfection of the plasmids containing serially deleted 5'upstream of the rat TRH gene ligated to luciferase gene, the transcription of luciferase gene was increased more than 3.2 fold with the plasmid pTRH(-600/84)Luc and pTRH(-113/84)Luc. However, the transcriptional activation was remarkably decreased less than 1.6 fold with pTRH(-77/84)Luc, pTRH(-47/84)Luc, and pTRH(6/84)Luc. The plasmid containing the sequence of -108/-79 did not show any significant activation in both of basal and TPA-stimulated transcription, whereas the plasmid containing the sequence of -70/-41 showed a slight but significant transcriptional activation by TPA. The plasmid containing the sequence of -114/-47 showed remarkable increase in basal transcription and TPA induced transcription of luciferase gene. Gel shift assay revealed that the oligonucleotides spanning -108/-79 and -70/-41 bound to c-Jun, whereas the oligonucleotides spanning -40/1, 1/30, 31/60, 61/84 did not bind. The oligonucleotide of -70/-41 bound to c-Jun with higher affinity compared to that of -108/-79. The one base pair mutant of -70/-41(deletion of C from the middle of TGACCTCA) bound to c-Jun with higher affinity, whereas the one base pair replaced mutant(C to G) bound with lower affinity compared to the wild type oligonucleotide. These results suggest that the rat TRH gene expression is stimulated by TPA to a smaller degree compared to that of other genes, and the two elements act cooperatively as TRE. The downstream TRE variant is mainly responsible for TPA response and c-Jun binding, and the upstream variant play a permissive role for transcriptional activation. The addition of one nucleotide C in the downstream element may be responsible for the relatively lower response of the rat TRH gene to TPA.
- Changes of Bone Turnover Markers after Treatment with Growth Hormone Therapy in Children with Growth Retardation.
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In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Ki Oak han, Duk Yoon Kim, Hyung In Yang
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J Korean Endocr Soc. 1994;9(4):344-349. Published online November 6, 2019
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- The effects of growth hormone(GH) deficiency and recombinant human GH replacement(0.5IU/kg per week) on bone mineral metabolism in 21GH-deficiency children were studied. All children had significantly reduction of bone density(Z score;-1.4+-0.71). After 1 month of therapy, the levels of serum insulin-like growth factor 1(IGF-1), osteocalcin(OC) and carboxyterminal propeptede of type 1 procollagen(PICP) were significantly elevated. But IGFBP-3 were not shown to change significantly. The changes in serum levels of PICP during the first month of recombinant human GH treatment were positively related to growth velocity, whereas the changes in IGF-1 and OC during the first month of therapy were not. We conclude that the recombinant human GH treatment caused significant modifications of mineral metablism and that the measurement of the changes of biochemical markers of bone metablism espacially PICP may be a useful tool in prediction improved growth velocity during long term GH replacement therpy.
- Clinical Characteristics of Acromegalic Patients in Korea.
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In Myung Yang
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J Korean Endocr Soc. 1994;9(4):290-306. Published online November 6, 2019
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- There was no nation-wide survey for acromegaly in Korea. To elucidate the incidence, clinical characteristics and the current status of diagnosis and treatment of acromegaly in Korea during the period from January 1988 to December 1992, we analyzed the survey protocols of 279 acromegalic patients which had been recorded in 24 university hospitals and 2 general hospitals. The estimated incidence was 1.4 per million individuals. The number of patients is not different in sex and the mean age was 42 years. The half of the patients were diagnosed at their forties and fifties. Enlargement of acral part is the most common sysptom(75%) and the next is dyspnea(69%) followed by headache(54%), excessive sweating(37%), diabetes mellitus(36%), visual disturbance(24%), hypertension(20%). The frequency of lumbar pain, visual disturbance and diabetes mellitus were higher, but that of hirsutism was lower than those reported in weatern studies. Oral glucose tolerance test was performed in only 46% of patients. Thirty four percent of them were diagnosed to have diabetes mellitus and 18% showed glucose intolerance. Forty two percent of patients had hyperphosphatemia and 36% of patients had an increased alkaline phosphatase activity. The GH suppression test by glucose was performed in only 56% of patients. The TRH or LHRH stimulation test was performed in only 29% and 14% of patients, respectively. The paradoxical response to TRH or LHRH was found in 53% and 33% of them, respectively. The somatostatin suppression test was carried out in only 17% of patients and the GH level was suppressed below 5 ng/ml in 49% of them. Bromocriptine suppression test was done in only 21% of patients and the GH level was normalized in 34.5% of them. To identify the location and size of pituitary tumor, computed tomography or magnetic resonance imaging was performed in only 52% of patients, and 78% of them had macroadenoma. About 10% of patients were not treated at all and 24% and 2% of patients were treated by only medication and radiotherapy, respectively. Normalization of GH level below 5 ng/ml was achieved in only 16.8% of patients who were considered to be cured completely after treatment. These data suggest that the incidence of acromegaly is relatively lower that that of european countries, and there are differences in the frequencies of clinical manifestations in Korean acromegalics. This survey also indicates that some essential diagnostic tests including endocrinologic evaluation were not performed in many cases, and the complete cure rate is significantly lower than that of western countries.
- Characterization of Cyclic AMP Response Element (CRE) in the Promoter of the Rat Thyrotropin Releasing Hormone (TRH) Gene.
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Woon Won Jung, In Myung Yang, Kwang Sik Seo, Seok Won Jung
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J Korean Endocr Soc. 1994;9(3):190-199. Published online November 6, 2019
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- We investigated whether the two variant elements of CRE(TGcCGTCA[5'CRE], TGACcTCA[3'CRE]) in the 5'flanking region of the rat TRH gene, which are different from the CRE consensus sequence(5'-TGACGTCA-3') by one base pair, are responsive to cAMP, and whether the one base pair difference is responsible for the degree of cAMP responsiveness of the gene. When CA 77 cells were stimulated with forskolin and isobutylmethylxanthine for 4 hours, the level of TRH mRNA was increased by only two fold. The transient gene expression study using serial 5'deletion of the TRH gene in PC12 cells showed that the region between-113 and-77, which includes 5'CRE, was crucial for the cAMP resonsiveness. When the plasmid, which contains the 30 bp oligonucleotide including either 5'CRE or 3'CRE ligated to the enhancerless RSV promoter, was transfected into PC12 cells, it did not significantly affect not only the basal transcription but cAMP responsiveness. The 65 bp oligonucleotide including both 5'CRE and 3'CRE, however, increased both of the basal transcription and cAMP-stimulated transcription by 2-3 fold. When the sequence of 5'CRE was converted to that of the CRE consensus by replacing one base pair, the cAMP responsiveness was increased by two fold although the basal transcription was not increased. The one base pair mutant of 3'CRE increased both of the basal and cAMP-stimulated transcription by 3-4 fold. These results suggest that there are the two variant CREs in rat TRH gene, which are relatively weak CRE compared to the CREs of other neuropeptide genes and cooperative for the activation of both the basal and cAMP-stimulated transcription. The one base pair difference of the variant CREs from the CRE consensus sequence is responsible for the weak responsiveness to cAMP.
- The Responses of Pituitary Hormones to the Combined Pituitary Stimulation Test in Hypogonadotropic Hypogonadism.
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In Myung Yang, Jeong Taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Young Kil Choi, Eun Kyung Park, Kyu Jeong Ahn
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J Korean Endocr Soc. 1994;9(2):93-107. Published online November 6, 2019
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- To classify the causes of hypogonadotropic hypogonadism in Korean patients, and to improve the endocrinologic evaluation for the disease, we retrospectively studied the clinical findings and result of combined pituitary stimulation test in 35 patients with hypogonadotropic hypogonadism. The following results were obtained.1) The ratio of male to female was 1.3:1, and the 50% of male patients was under 20 years of age and the 20% of female patients in 30th decades. 2) The chief complaints of male patients on the admission were the failure of secondary sexual characteristics(95.0%) and loss of hair(5.0%), those of female patients were amenorrhea(46.7%), infertility(26.7%), failure of secondary characteristics(13.3%) and loss of hair(13.3%). 3) The causes of male hypogonadotropic hypogonadism were craniopharyngioma(35.0%), idiopathic(30.0%), Kallmann's syndrome(15.0%), pituitary adenoma(10.0%) and germinoma(5.0%), and those of female hypogonadotropic hypogonadism were prolactinoma(13.3%), Sheehan's syndrome(26.6%), pituitary adenoma(6.7%), tuberculous granuloma(6.7%), germinoma(6.7%), idiopathic hypogonadotropic hypogonadism(40.0%).4) The responses of LH and FSH to GnRH test were absent or markedly blunted in diffuse pituitary diseases such as pituitary tuberculous granuloma, pituitary macroadenomas, Sheehan's syndrome. However those were also absent or blunted in Cushing's disease and hypothalamic disease such as Kallmann's syndrome, germinoma, craniopharyngioma, idiopathic hypogonadotropic hypogonadism. 5) The responses of LH, FSH increased after repeated injection of GnRH in a patient with germinoma. 6) In diffuse destructive pituitary diseases such as Sheehan's syndrome, nonfunctioning macroadenomas, tuberculous granuloma, large prolactinoma, the combined deficiency of pituitary hormones other than gonadotropins was observed. 7) In many cases with hypothalamic diseases, the combined defects of pituitary hormone response were also seen.These data suggest that GnRH test is not always useful to localize the lesion between pituitary and hypothalamus, and combined pituitary stimulation test revealed defects of pituitary hormones other than gonadotropin in various hypothalamic diseases.Therefore repeated GnRH test would be useful for the differential diagnosis, and CRH test and GRH test would be necessary to demonstrate whether pituitary abnormality is present.
- Oncogenic Osteomalacia.
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In Myung Yang, Seung Joon Oh
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J Korean Endocr Soc. 1994;9(1):1-4. Published online November 6, 2019
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- No abstract available.
- Human IGF-I gene expression in normal and thyroid tumor tissues.
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Sung Woon Kim, Hyun Ha Jang, Sang Mee Park, Deog Yoon Kim, Jeong Taek Woo, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Suck Hwan Koh, Sung Wha Hong, Young Kil Choi
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J Korean Endocr Soc. 1993;8(4):414-421. Published online January 1, 2001
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- No abstract available.
- Effect of ipriflavone on the lumbodorsal pain in osteoporosis.
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Jeong Taek Woo, Deok Yoon Kim, In Myung Yang, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1993;8(3):340-346. Published online January 1, 2001
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- No abstract available.
- Expression of type 1?collagen mRNA of osteoblast like(MC3T3-E1) celss to sodium fluoride.
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Jeong Taek Woo, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi, Kwang Sik Seo, Kyu Rhim Chung, Jeung Bin Hwang
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J Korean Endocr Soc. 1993;8(3):334-339. Published online January 1, 2001
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- No abstract available.
- A clinical study of thyrotoxic periodic paralysis.
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Sung Yi Kang, Sung Hoon Kim, Duk Yoon Kim, Jeong Taek Woo, In Myung Yang, Sung Woon Kim, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1993;8(1):19-26. Published online January 1, 2001
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- No abstract available.
- Effect of cilostazol in diabetic patients with vascular complication .
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Kyu Nam Lee, Jeong Tack Woo, Duck Yoon Kim, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1992;7(4):373-378. Published online January 1, 2001
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- No abstract available.
- Effects of human growth hormone treatment in healthy older female.
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Jeong Tack Woo, Deog Yoon Kim, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi, Jong Eun Park
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J Korean Endocr Soc. 1992;7(4):352-357. Published online January 1, 2001
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- No abstract available.
- Apolipoprotein E genotypes in patients with diabetes, cerebrovascul- ar accident, and acute myocardial infarction.
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Sung Yi Kang, Jeong Tack Woo, Sung Woon Kim, in Myung Yang, Jin Woo Kim, Young Seol Kim, Ke\wang Won Kim, Young Kil Choi, Jung Ryung Paeng
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J Korean Endocr Soc. 1992;7(3):273-279. Published online January 1, 2001
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- No abstract available.
- Review of clinical characteristics of primary hyperparathyroidism.
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Hyung Keun Chung, Deog Yoon Kim, Jeong Taek Woo, Sang Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1992;7(3):234-242. Published online January 1, 2001
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- No abstract available.
- Expression of c-erb A mRNA according to thyroid function status.
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Young Sil Ju, Jeong Taek Woo, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi, Sang Mi Park
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J Korean Endocr Soc. 1992;7(1):24-30. Published online January 1, 2001
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- No abstract available.
- Role of hepatitis B infection in pathogenesis of autoimmune thyroid disease.
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Hyung In Yang, Jeong Taek Woo, Seong Wun Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1991;6(4):348-352. Published online January 1, 2001
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- No abstract available.
- Molecular biologic research in the thyrotropin releasing hormone.
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In Myung Yang
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J Korean Endocr Soc. 1991;6(3):271-275. Published online January 1, 2001
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- No abstract available.
- Effect of fluoride and vandate on the osteoblast MC3T3-E1 function.
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Jung Taek Woo, Hyun Koo Yoon, Young Seol Kim, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Kwang Won Kim, Young Kil Choi, Kwang Sik Seo
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J Korean Endocr Soc. 1991;6(2):157-162. Published online January 1, 2001
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- No abstract available.
- A clinical study on 79 cases of lymphocytic thyroiditis by fine needle aspiration.
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Kyung Jin Kim, Jeong Taek Woo, Sung Woon Kim, In Myung Yang, Jin Woo Kim, Young Seol Kim, Kwang Won Kim, Young Kil Choi
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J Korean Endocr Soc. 1991;6(1):38-44. Published online January 1, 2001
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- No abstract available.
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