Hormonal Regulation of Insulin-Like Growth Factor Binding Protein Secretion by a Bovine Mammary Epithelial Cell Line

Kim, W.Y.,Chow, J.C.,Hanigan, M.D.,Calvert, C.C.,Ha, J.K.,Baldwin, R.L. Asian Australasian Association of Animal Productio 1997 Animal Bioscience Vol.10 No.2

A mammary epithelial cell line (MAC-T) established as a model for lactation was utilized to identify and characterize effects of various hormones upon insulin-like growth factor binding protein secretion. Ligand and immunoblot analyses of conditioned media indicated that insulin-like growth factor binding protein-2 was secreted by MAC-T cells. Insulin-like growth factor-I stimulated insulin-like growth factor binding protein-2 secretion in a dose-dependent manner, but prolactin and bovine somatotropin did not alter insulin-like growth factor binding protein-2 secretion. Insulin increased and cortisol decreased insulin-like growth factor binding protein-2 secretion. Effects of insulin-like growth factor-I on insulin-like growth factor binding protein-2 secretion support previous studies using primary cultures of bovine mammary cells and bovine fibroblasts. Effects of cortisol and insulin on insulin-like growth factor binding protein-2 secretion may be explained by changes in protein synthesis. In addition, supraphysiological doses of insulin can cross-react with the insulin-like growth factor-I receptor and stimulate insulin-like growth factor binding protein-2 secretion. MAC-T cells provide a model system to study mechanisms that regulate local insulin-like growth factor-I bioactivity.

성장호르몬 결핍증 진단에 있어서 혈중 insulin-like growth factor-I 및 insulin-like growth factor binding protein-3 농도의 진단적 유용성에 대한 연구

지근하,이정녀,정우영 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.12

Purpose:This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. Methods:Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). Results:The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3, we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 14 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. Conclusion:We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control. (Korean J Pediatr 2008;51:1329-1335) Purpose:This study aimed to determine the best cutoff line for insulin-like growth factor (IGF)-I and insulin-like growth factor binding protein (IGFBP)-3 to discriminate between growth hormone deficiency (GHD) patients and the control group. Methods:Two hundred thirty subjects with normal controls (129 boys and 101 girls, aged 7-15 years), 14 patients with complete GHD (12 boys and 2 girls), and 17 patients with partial GHD (9 boys and 8 girls) were studied. IGF-I serum concentrations were measured by radioimmunoassay (RI), and IGFBP-3 concentrations were measured by immunoradiometric assay (IRMA). Results:The receiver operating characteristic (ROC) plot analysis showed that the best IGF-I and IGFBP-3 cutoff line was at -1 standard deviation (SD). By comparing IGF-I serum levels of GHD children within 1 SD of normal control, we determined the sensitivity (S) (87.5-100%) and specificity (Sp) (80-84.6%) according to the age group. For IGFBP-3, we determined the following values: S (58.7-85.7%) and Sp (79.2-85.5%). Eleven of 14 patients with complete GHD (78.5%) and 16 of 17 patients with partial GHD (94.1%) had IGF-I concentrations equal to or below -1 SD of the control group mean. Ten of 12 complete GHD children (83.3%) and 13 of 17 partial GHD children (76.5%) had IGFBP-3 concentrations equal or below -1 SD of the control group mean. Conclusion:We conclude that the measurement of IGF-I and IGFBP-3 concentrations might provide essential supplementary data in the diagnostic evaluation of patients with GHD. Our results support the need to use cutoff lines based on below -1 SD of the control. (Korean J Pediatr 2008;51:1329-1335)

만성신부전 환자에서 장기간 투석요법 전후의 Insulin-like Growth Factor 및 Insulin-like Growth Factor Binding Proteins 의 변화

이경훈(Kyoung Hoon Lee),문치영(Chi Young Moon),김원(Won Kim),이대열(Dae Yeol Lee),박성광(Sung Kwang Park),강성귀(Sung Kyew Kang) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.2

N/A The insulin-like growth factor-I(IGF-I) is a hormone that has growth stimulation and metabolic effects. Insulin-like growth factor binding proteins (IGFBPs) were known to be the most important factors that affect bioavailability of IGF. Thereby, the changes of IGFBPs may affect the bioavailability of IGF-I. Because growth hormone/IGF system may be affected by dialysis therapy, the changes of GH, IGF-1, IGFBPs levels after dialysis therapy can affect the bioavailability of IGF. To evaluate the changes of serum levels of IGF-I and IGFBP-3 after long-term dialysis therapy, we measured the serum IGF-I and IGFBP-3 levels in the patients on hemodialysis and on peritoneal dialysis. Eight: patients undergoing peritoneal dialysis, 10 patients undergoing hemodialysis, and age-matched 10 normal control patients were studied. In patients on hemodialysis, the mean serum level of IGF-I before hemodialysis was 90.6±9.0ng/mL, and after long-term hemodialysis was 130.9±31.0ng/ mL. The mean serum level of IGFBP-3 before hemodialysis was 14,549±7,815 μg/L, and after longterm hemodialysis was 5,726±883 μg/L. There were no significant changes of serum IGF-I and IGFBP-3 levels after long-term hemodialysis therapy. In patients on peritoneal dialysis, the mean serum level of IGF-I before peritoneal dialysis was 169.8±20.5ng/ mL, and after long-term peritoneal dialysis was 242.6±37.6ng/mL. The mean serum level of IGFBP- 3 before peritoneal dialysis was 10,272±885 μg/L, and after ling-term peritoneal dialysis was 8,604±1,721 μg/L. There were no significant changes of serum IGF-I and IGFBP-3 levels after long-term peritoneal dialysis. We found that the level of IGF-1 before hemodialysis was lower then that of normal control group and the level of IGFBP-3 before hemodialysis or peritoneal dialysis was higher then that of normal control group. Our results suggested that the blood levels of growth hormone, IGF-I and IGFBP-3 may not be significantly affected by long-term dialysis therapy.

한국 소아 및 청소년에서 혈중 유리 insulin-like growth factor-I 농도치와 임상적 의의

정영희,정우영 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.1

Purpose:The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)- 3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods:Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results:The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion:In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age. (Korean J Pediatr 2008;51:47-53) Purpose:The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)- 3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods:Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results:The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion:In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age. (Korean J Pediatr 2008;51:47-53)

인간 황체화과립막세포에서 변형성장인자-α가 인슐린유사성장인자-2와 인슐린유사성장인자 결합단백질-1, 3의 분비 및 표피성장인자 수용체의 발현에 미치는 영향

강은희 ( Eun Hee Kang ),홍석호 ( Seok Ho Hong ),조준식 ( Jun Sik Cho ),김성훈 ( Sung Hoon Kim ),채희동 ( Hee Dong Chae ),김정훈 ( Chung Hoon Kim ),강병문 ( Byung Moon Kang ),남주현 ( Joo Hyun Nam ) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.12

Objective : To investigate the effects of transforming growth factor (TGF)-α on insulin-like growth factor (IGF)-α, insulin-like growth factor binding protein (IGFBP)-1, and 3 secretion and epidermal growth factor (EGF) receptor expression in cultured hum

Influence of Gender on Serum Growth Hormone, Insulin-Like Growth Factor-I and Its Binding Protein-3 during Aging

Chiou-Meei Lin,Yeou-Lih Huang,Zu-Yau Lin 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.3

Purpose: The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects. Materials and Methods: Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into ≤ 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay. Results: IGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women ≤ 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 ± 0.039404) than men of same age group (0.228326 ± 0.050979, p < 0.01) and women ≤ 50 years (0.247667 ± 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women. Conclusions: The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age. Purpose: The serum concentrations of insulin-like growth factors-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and growth hormone (GH) are related to body composition, function and metabolism, and are influenced by the aging process. This study was to investigate the influence of gender on serum concentrations of IGF-I, IGFBP-3 and GH in middle and old age subjects. Materials and Methods: Sixty healthy volunteers (male 35, female 25, 36-70 years) were divided into ≤ 50 and > 50 years groups, based on gender. Women > 50 years were post-menopause. IGF-I, IGFBP-3, and GH were determined by immunoradiometric assay. Results: IGF-I was shown to be negatively correlated with age (women r = -0.62, p < 0.001; men r = -0.38, p < 0.05), whereas there was no correlation between IGF-I and GH values. Women > 50 years showed a significant reduction in IGF-I values than women ≤ 50 years (p < 0.01). Women > 50 years showed smaller IGF-I/IGFBP-3 molar ratios (0.177998 ± 0.039404) than men of same age group (0.228326 ± 0.050979, p < 0.01) and women ≤ 50 years (0.247667 ± 0.069411, p < 0.01). Age was shown to positively correlate with GH/IGF-I (r = 0.49, p < 0.05) and GH/IGFBP-3 ratios (r = 0.40, p < 0.05) in women. Conclusions: The influence of aging on serum concentrations of IGF-I is more remarkable in women than in men. Menopause causes reduction of IGF-I/IGFBP-3 molar ratio. Women have the trend of progressive hypoactivity of GH to stimulate IGF-I and IGFBP-3 secretions with age.

특발성 저신장증 환아의 혈중 Insulin-like Growth Factor-I 및 Insulin-like Growth Factor Binding Protein-3 농도

배원진,정지미,정우영 대한소아내분비학회 2008 Annals of Pediatirc Endocrinology & Metabolism Vol.13 No.2

Purpose : The aim of present study was to compare the mean serum levels of Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding protein-3 (IGFBP-3) according to the Korean standard growth chart especially in children with idiopathic short stature. Methods : Serum levels of IGF-I and IGFBP-3 were determined in 454 children (252 boys and 202 girls; ages 7-15 yr), grouped into two, according to their height below 10 percentile (idiopathic short stature) and 25-50 percentile based on growth chart- 1998 reported by Korean Society of Pediatrics. Serum levels of IGF-I were measured by RIA method and serum levels of IGFBP-3 were measured by IRMA method. Results : Mean serum levels of IGF-I and IGFBP-3 were lower in below 10 percentile group compared with those of 25-50 percentile group in both sexes. In some age groups, the differences between two groups revealed statistical significance. The difference of serum levels according to growth channel showed more prominence in IGF-I compared than IGFBP-3. Significant statistical correlations were demonstrated in all study groups between serum IGF-I and IGFBP-3 levels according to the age, respectively. Conclusion : Our results strongly suggest that mean serum levels of IGF-I and IGFBP-3 in children with idiopathic short stature were lower than those of control group.

성장인자들이 인간의 황체화 과립막세포에서의 인슐린유사 성장인자 및 그 결합단백질의 생산에 미치는 영향

김정구(JK Kim),김석현(SH Kim),최영민(YM Choi),신창재(CJ Shin),문신용(SY Moon),장윤석(YS Chang),이진용(JY Lee) 대한산부인과학회 1996 Obstetrics & Gynecology Science Vol.39 No.2

Intraovarian polypeptide growth factors such as insulin-like growth factors(IGFs), epidermal growth factor(EGF), transforming growth factor beta(TGF B) and basic fibroblastic growth factor(bFGF) have been implicated as potentiators or mediators of gonadotropin action in the ovarian cycle. This study was undertaken to evaluate the effect of EGF, TGF B and bFGF on the production of IGFs and IGF-binding proteins(IGFBPs) in human luteinizing granulosa cells cultures in serum free medium. IGFs were measured by double antibody radioimmunoassay and IGFBPs by Western ligand blotting. No immunoreactive IGF-I was detectable in all conditioned media of luteinizing granulosa cells. IGF-I(1-100 ng/ml) and bFGF(100 ng/ml) were found to stimulate IGFBP-3 and IGFBP-2 production significantly. Also bFGF had similar effect on the IFG-II production but IFG-I had not show this effect. On the other hand IGFBP-2, IGFBP-3 and IGF-II production were significantly inhibited by TGF B(1-10 ng/ml). EGF was shown to have biphasic effect on the IGFBPs production and stimulated IGF-II production at a concentration of 10-100 ng/ml. Treatment of luteininzing granulosa cells cultures with IGF-I(10 ng/ml) and TGF B(0.1 ng/ml) significantly enhanced IGFBP-3 levels in conditioned media but exerted no significant effect on IGFBP-2 and IGF-II levels. IGF(10 ng/ml) plus TGF B(1 ng/ml) significantly inhibited thses IGFBPs production but resulted in significant increase in IGF-II production. Coincubation of luteininzing granulosa cells with IGF, EGF and/or TGF B significantly(p<0.005) stimulated TGFBP-2, IGFBP-3 and IGF-II production. Our data indicate that IGF-I induced increases in IGFBPs may play an important role in controlling local cell responsiveness to this growth factor and that axis between IGF-II, IGFBP and other growth factors may present.

Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

Bae, Il-Hong,Park, Jin Woo,Kim, Dae-Yong Dove Medical Press 2014 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.9 No.-

<P>Exogenous administration of growth factors has potential benefits in wound healing; however, limited percutaneous absorption, inconsistent efficacy, and the need for high doses have hampered successful clinical use. To overcome these restrictions, we focused on the development of a topical formulation composed of highly skin-permeable multimeric nanocomplex of growth factors. In the present study, we fused low-molecular-weight protamine (LMWP) with epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-I), and platelet-derived growth factor A ligand (PDGF-A) (producing recombinant [r]LMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A, respectively) via genetic modification. Then, we used in vitro cell proliferation studies to assess the biological activity and the benefits of the combination. The LMWP-conjugated growth factors were complexed with low-molecular-weight heparin (LMWH) and formulated with Poloxamer 188 as a delivery vehicle. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether the LMWP-conjugated growth factor nanocomplex formulations accelerated the healing of full-thickness wounds in mice. The LMWP-conjugated growth factors were biologically equivalent to their native forms, and their combination induced greater fibroblast proliferation. rLMWP-EGF showed significantly enhanced permeability and cumulative permeation, and the rates for rLMWP-IGF-I and rLMWP-PDGF-A, across excised mouse skin, were 124% and 164% higher, respectively, than for the native forms. The LMWP-fused growth factors resulted in formation of nanocomplexes (23.51±1.12 nm in diameter) in combination with LMWH. Topical delivery of growth factors fused with LMWP accelerated wound re-epithelialization significantly, accompanied by the formation of healthy granulation tissue within 9 days compared with a free–growth factor complex or vehicle. Thus, the LMWP-conjugated growth factor nanocomplex can induce rapid, comprehensive healing and may be a candidate wound-healing therapeutic.</P>

소의 theileriosis가 성장 hormone과 insulin-like growth factor-I에 미치는 영향

백병걸,변선윤,이존화,이호일,Baek, Byeong-kirl,Byoun, Sun-youn,Lee, John-wha,Lee, Ho-ill 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2

Bovine theileriosis caused by Theileria sergenti is the tick-borne intraery- throcytic piroplasmosis, that occurs in most regions of Korea. It results in severe economic losses on a farm caused by anemia, milk production loss, abortion and death. This study was undertaken to confirm the effects of the growth hormone and the insulin-like growth factor-I which are associated in the growth of cattle infected by T sergenti. The blood of one hundred and twenty ten-month Holstein was collected and the prepared blood smear was stained with acridine orange to investigate their parasitemia. And the hematological profiles were observed. According to the value of the hematocrit, they were categorized into four groups : Group 1 was under 20 percent, groups 2 and 3 were from over 21 to under 30 percent and from over 31 to under 35 percent and group 4 was over 36 percent. As the value of the hematocrit decreased, parasitemia(%) in erythrocytes was observed to increase(Y=-1.064X + 30.537, r=0.660). The amounts of the growth hormone and the insulin-like growth factor-I in the serum were measured by the radioimmunoassay. The growth hormone in serum of the group 1, group 2, group 3 and group 4 were observed as $0.238{\pm}0.043nmol/l$, $0.21{\pm}0.024nmol/l$, $0.366{\pm}0.035nmol/l$ and $0.646{\pm}0.223nmol/l$, respectively. The quantitative of the insulin-like growth factor-I in the same groups were observed also as $209.686{\pm}18.94ng/ml$, $250.9{\pm}12.609ng/ml$, $279.3{\pm}8.883ng/ml$ and $365.9{\pm}22.45ng/ml$, respectively. It can be concluded that the growth hormone and the insulin-like growth factor-I were observed to decrease in severe anemia due to theileriosis.