• Clinical and Experimental Pediatrics
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• v.49 no.5
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• pp.552-557
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• 2006

Purpose : The recent results observed in precocious puberty and the hope that interrupting puberty might increase adult height have led to an attempt to use GnRH agonist(GnRHa) in children with premature puberty and a poor growth prognosis. We aimed to analyze the growth promoting effect of GnRHa in girls with early puberty and low predicted adult height(PAH). Methods : Thirty six girls were recruited. They were grouped according to the GnRHa treatment period(group 1>6 mo, n=18; group 2<6 mo, n=18). The following variables were analyzed before and after GnRHa treatment : chronological age(CA), bone age(BA), ${\Delta}age$(CA-BA), height, target height (TH), PAH, serum IGF-1, IGFBP-3. Results : Duration of the GnRHa treatment was $0.89{\pm}0.81yr$($1.37{\pm}0.92yr$ in group 1, and $0.41{\pm}0.08yr$ in group 2). Before treatment, none of the variables were different between the two groups. There were no differences in the following variables the between two groups at the end of treatment : CA, BA, ${\Delta}age$, PAH, serum IGF-1, IGFBP-3. But, growth velocity(GV) and PAH increment during treatment were significantly reduced in group 1. Compared with initial PAH, PAH at the end of treatment was significantly increased($3.7{\pm}3.2cm$). The last serum levels of IGF-1 and IGFBP-3 were lower than those before treatment. Conclusion : Even though last PAH didn't approach TH, short term GnRHa administration in early puberty with low predicted PAH was somewhat effective. But, GnRHa administration suppressed the growth hormone-IGF-1 axis. Therefore, it is recommended that growth hormone(GH) should be used in combination with GnRHa.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.9
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• pp.1244-1251
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• 2008

The aim of the present study was to delineate the expression and secretion of insulin-like growth factor (IGF) system components by pig liver cells. Hepatocytes were prepared from 3-wk-old weanling piglets following a two-step collagenase perfusion procedure, after which the cells were incubated for 24 or 48 h at a density of $2{\pm}10^5$ cells per 35-mm dish in 2-ml Williams' medium E. The cells were found to express the genes encoding IGF-I, IGF-binding proteins (IGFBPs)-2 and -3 and acid-labile subunit (ALS) by reverse transcription-polymerase chain reaction (RT-PCR) following the culture. However, IGF-I was localized to hepatocytes by immunohistochemical analysis, whereas IGFBP-3 was localized to endothelial cells, but not to hepatocytes. This indicated that the IGFBP-3 gene expression detected by RT-PCR was likely to have been contributed by unidentified non-parenchymal cells that had not been removed during the hepatocyte preparation. The conditioned culture medium (CCM) of the cells contained immunoreactive IGF-I and IGF-II, with the latter being seven-fold more abundant than the former. The CCM also contained 43-, 40-, 34-, 31-kDa doublet and 26-kDa IGFBPs as examined by Western ligand blotting. The 40-, 34- and 31-kDa doublet IGFBPs were approximately three-fold as abundant as the 43- and 26-kDa IGFBPs. Moreover, the 43- and 40-kDa doublet and the 34-kDa IGFBPs were immunoprecipitable with IGFBP-3 and IGFBP-2 antibodies, respectively. Overall, these results are similar to those known in the rat, which suggests that the IGF system components are likely to be expressed and secreted in pig liver in a manner similar to that in rat liver.

• Development and Reproduction
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• v.20 no.3
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• pp.179-185
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• 2016

The insulin-like growth factor (IGF) pathway is a key signal transduction pathway involved in cell proliferation, migration, and apoptosis. In dairy cows, IGF family proteins and binding receptors, including their intracellular binding partners, regulate mammary gland development. IGFs and IGF receptor interactions in mammary glands influence the early stages of mammogenesis, i.e., mammary ductal genesis until puberty. The IGF pathway includes three major components, IGFs (such as IGF-I, IGF-II, and insulin), their specific receptors, and their high-affinity binding partners (IGF binding proteins [IGFBPs]; i.e., IGFBP1-6), including specific proteases for each IGFBP. Additionally, IGFs and IGFBP interactions are critical for the bioactivities of various intracellular mechanisms, including cell proliferation, migration, and apoptosis. Notably, the interactions between IGFs and IGFBPs in the IGF pathway have been difficult to characterize during specific stages of bovine mammary gland development. In this review, we aim to describe the role of the interaction between IGFs and IGFBPs in overall mammary gland development in dairy cows.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.865-870
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• 2005

Purpose : The use of growth hormone(GH) to promote growth in normal short children without classical GH deficiency is controversial. Numerous foreign studies have shown the effects of GH therapy in children with idiopathic short stature(ISS) whereas few has been interested in Korea. Therefore, this study is designed to investigate the effects of GH therapy on ISS by observing correlations and changes among various growth parameters such as, insulin-like growth factor-I(IGF-I) and insulin-like growth factor binding protein-3(IGFBP-3). Methods : This study was conducted retrospectively with 15 children with ISS in Chungbuk National University Hospital in Korea. Mean age was $11.44{\pm}2.81$ and the children were treated with 0.66 IU/kg/wk dosage of GH for 1 or 2 years. Also, the growth parameters before and after the GH therapy were observed. Results : Height standard deviation score(HT-SDS) was increased from $-1.85{\pm}0.70$ to $-1.58{\pm}0.56$ at 1 year and to $-1.21{\pm}0.37$ at 2 years after GH therapy. Predicted adult height standard deviation score(PAH-SDS) was also increased from $-2.10{\pm}0.52$ to $-1.67{\pm}0.59$ at 1 year, and to $-0.96{\pm}0.60$ at 2 years. Serum IGF-I and IGFBP-3 levels were significantly increased after 1 year and marginally increased after 2 years of GH therapy. Conclusion : It is concluded that GH therapy has growth promoting effect. The significant increase in IGF-I and IGFBP-3 levels during the GH therapy suggests that IGF-I and IGFBP-3 are useful predictors of response to the use of GH therapy. It is expected that larger patient samples would provide more reliable information about the effect of GH therapy.

• Journal of Nutrition and Health
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• v.35 no.2
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• pp.192-200
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• 2002

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated. CLA has anticancer activity in a variety of animal cancer models, and cis-9, trans-11 (c9t11) and trans-10, cis-12(t10c12) CLA are the most predominant isomers present in the synthetic preparations utilized in these animal studies. To compare the ability of c9t11, t10c12 and an isomeric mixture of CLA to inhibit TSU-Prl cell growth, cells were incubated in a serum-free medium with various concentrations of these fatty acids. The isomeric mixture inhibited cell growth in a dose-dependent manner (1-3 $\mu$M) with a 41 $\pm$ 1% inhibition observed at 3 $\mu$M concentration after 48 hours. T10c12 also inhibited cell proliferation in a dote-dependent manner, However, the efficacy and potency of this isomer was much greater than that of the isomeric mixture with a 49 $\pm$ 2% inhibition observed at 0.3 $\mu$M concentration after 48 hours. By contrast, c9t11 slightly increased cell proliferation. To determine whether the growth-inhibiting effect of CLA is related to the changes in production of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) by these cells, serum-free conditioned media were collected. Immunoblot analysis of conditioned media using a monoclonal anti-IGF-II antibody showed that both the isomeric mixture and t10c12 inhibited secretion of both mature 7,500 Mr and higher Mr forms of pro IGF-II, whereas c9t11 had no effect. Ligand blot analysis with 125I-IGF-II revealed the presence of two types of IGFBPs : 24,000 Mr IGFBP-4 and 30,000 Mr IGFBP-6. The production of IGFBP-4 slightly decreased at the highest concentrations of the isomeric mixture and t10c12. These results indicate that CLA inhibits human prostate cancer cell growth, an effect largely due to the action of t10c12. The growth inhibition may result, at least in part, from decreased production of IGF-II and IGFBP-4 by these cells.

• Journal of Nutrition and Health
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• v.36 no.3
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• pp.270-279
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• 2003

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid (LA) and exhibits anticarcinogenic activity in a variety of animal models. We have previously observed that CLA inhibited the growth of Caco-2 cells, a human colon adenocarcinoma cell line. The present study was performed to determine whether the growth inhibitory effect of CLA is related to change in secretion of IGF- II and/or IGF-binding proteins (IGFBPs) that have been shown to regulate Caco-2 cell proliferation by an autocrine mechanism. Cells were incubated in serum-free medium with various concentrations of CLA or linoleic acid (LA). Immunoblot analysis of 24-hours, serum-free, conditioned medium using a monoclonal anti-IGF-IIantibody revealed that Caco-2 cells secreted both mature 6,500 Mr and higher Mr forms of pro IGF-II. The levels of pro IGF-II and mature IGF-IIwere decreased by 43 $\pm$ 2% and 53 $\pm$ 6%, respectively by treatment with 50 $\mu$ M CLA. LA slightly increased pro IGF- II levels. Results from Northern blot analysis showed that CLA decreased IGF-II mRNA levels at 50 $\mu$ M concentration suggesting that CLA regulation of IGF-II protein expression occurs partly at the transcriptional level. Ligand blot analysis of conditioned media using 1251-IGF-II revealed that CLA slightly decreased IGFBP-2 levels and increased IGFBP-4 levels. We confirmed our previous results that CLA inhibited cell growth in a dose-dependent manner but LA slightly increased cell growth. Exogenous IGF-II mitigated the growth inhibitory effect of CLA. These results indicate that the growth inhibitory effect of CLA may be at least in part mediated by decreasing IGF-II and IGFBP-2 secretion and increasing IGFBP-4 secretion in Caco-2 cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.555-566
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• 2018

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and ${\beta}-catenin$; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.5
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• pp.659-665
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• 2000

A nitrogen (N) balance trial was conducted to examine the effect of N deprivation on subsequent N retention, blood urea nitrogen (BUN) and IGF-I levels and the ratio of IGF binding protein (IGFBP)-3 to IGFBP-l and -2. Pigs in treatment (T) 1 were given diet A (2.39% N) and those in T2 and T3 were given diet B (1.31% N) and excreta were collected (period 1 (P1)). Pigs in T1 continued to receive diet A while diets for T2 and T3 were changed to diets A and C (2.74% N), respectively. The excreta were collected for two more periods (P2 and P3). During P1, pigs in T2 and T3 retained 50% less N (p<0.001) than those in T1. However, pigs provided T2 (p<0.01) and T3 (p<0.05) retained more N than those assigned to T1 during P2. Pigs in T3 tended to retain more (p=0.10) N than those receiving T2 for the same period. The BUN values were lower (p<0.05) for pigs assigned to T2 and T3 than T1 during P1 and P2. Both IGF-I and IGFBP ratios of pigs assigned to T1 were higher (p<0.05) than those given T2 and T3 during P1 but no differences were found during P2 and P3.

• Fisheries and Aquatic Sciences
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• v.22 no.9
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• pp.19.1-19.10
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• 2019

We investigated the insulin-like growth factor 1 (IGF-1)/AKT signaling pathway involved in muscle formation, growth, and movement in the adductor muscle of triploid Pacific oyster, Crassostrea gigas. Large and small triploid oysters (LTs and STs) cultured under identical conditions were screened, and the signaling pathways of individuals with superior growth were compared and analyzed. mRNA and protein expression levels of actin, troponin, tropomyosin, and myosin, proteins important in muscle formation, were higher in LTs compared with STs. Expression levels of IGF-1, IGF binding protein (IGFBP), and IGFBP complex acid-labile subunit were also higher in LTs compared with STs. Phosphorylation of the IGF receptor as well as that of AKT was high in LTs. In addition, the expression of phosphomammalian target of rapamycin and phospho-glycogen synthase kinase $3{\beta}$ was increased and the expression of Forkhead box O3 was decreased in LTs. Therefore, we suggested that the IGF-1/AKT signaling pathway affects the formation, growth, and movement of the adductor muscle in triploid oysters.

• Korean Journal of Food Science and Technology
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• v.46 no.3
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• pp.358-363
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• 2014

Herbs have active components that promote the growth rate of both animals and human. The KI-180 and KI-188 calcium food formulae contain Acanthopanacis cortex, Bombysis corpus and hoelen, seaweed calcium, chlorella extract, spirulina, colostrum powder, and other natural and functional components. We evaluated the growth-promoting effects of these formulae by analyzing the weight, femur and backbone, alkaline phosphatase, osteocalcin, testosterone, insulin-like growth factor (IGF)-1, and IGF binding protein-3 (IGFBP-3) of growing rats. Growing rats administered with KI-180 and KI-188 calcium showed the increase of body weight, body length, and femur weight and length of growing rats. In addition, administration of KI-180 and KI-188 calcium increased the alkaline phosphatase activity, the levels of osteocalcin and the growth hormones IGF-1 and IGFBP-3 of growing rats. The impact of KI-180 and KI-188 calcium on the physical development of growing rats suggests that the incorporation of these food formulae in the diets of growing children may promote the physical development.