• Korean Journal of Medicinal Crop Science
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• v.23 no.1
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• pp.1-7
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• 2015

This study was carried out to investigate the effects of the Cirsium japonicum var. ussuriense (C. japonicum) extract on serum level of hormones from induced osteoporosis by ovariectomized rats. Two month-old rats were ovariectomized (OVX), remained untreated for 8 weeks, and were subsequently administered C. japonicum (200 mg/kg) every day for 8 weeks. We examined the effects of treated C. japonicum on ovariectomy-related changes in Insulin-like Growth Factors (IGF), Insulin-like Growth Factor binding protein-3 (IGBF-3), Estrogen, Calcium, and Phosporus. After 8 weeks, the serum levels of IGF-I, -II, and IGFBP-3 were higher presented as compared to the other two groups (P < 0.05), in the C. japonicum extract treatment on OVX rats. There were differences between OVX and C. japonicum extract treated OVX rats in serum levels of $Ca^{2+}$, but $Ca^{2+}$ levels for the normal group was higher than for the other two groups. The C. japonicum extract increased both serum IGFs and IGFBP-3 levels on induced osteoporotic rat by ovariectomized. Thus, these results revealed that the C. japonicum extract is a possible role for improvement of osteoporosis induced-ovariectomized rats and has a great potential as an alternative tool for the treatment of osteoporosis.

• Proceedings of the KSAR Conference
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• 2005.06a
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• pp.47-54
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• 2005

In boars, unlike the cases in males of other species, gonadal hormones suppress voluntary feed intake. for this reason, barrows, compared with gilts or boars, eat too much feed resulting in excessive fat deposition. Two experiments were performed in the present study to investigate the effects of implantation of Revalor H[Experiment(Exp.) I: 140mg trenbolone acetate(a synthetic androgen) + 14mg estradiol-$17\beta(E_{2}\beta)$] and Compudose(Exp. II; 24mg $E_{2}\beta$) on growth efficiency, carcass characteristics and circulating concentrations of IGF-I and IGF-binding protein-3(IGFBP-3). In Exp. I, sixty-four cross-bred finishing barrows weighing approximately 60kg were randomly divided into eight pens under a 2[control vs Revalor implant] $\times$ 2(ad libitum vs $80\%$ ad libitum feeding) $\times$2[control($103\%$ NRC-recommended level) vs low-energy($87\%$ NRC recommendation) diet] arrangement of treatments. In Exp. II, effects of Compudose were studied using 80 finishing barrows(10 animals/pen). In both Exps., all the animals were slaughtered at 100- to 110-kg body weight. Both Revalor and Compudose implants caused a decrease in feed intake and backfat thickness without affecting major physicochemical characteristics of the carcass and an increase in circulating IGF-I concentration. Moreover, Revalor implant exhibited greater effects than restricted feeding, low-energy diet, or Compudose in these variables. In addition, Revalor implantation suppressed weight gain, but enhanced the feed efficiency without exhibiting any interaction with the diet or feeding. In summary, results suggest that 1) both androgen and estrogen suppress voluntary feed intake and backfat deposition and enhance IGF-I secretion and 2) these effects of the gonadal steroid hormones in growth are likely to be mediated, in part, by IGF-I in finishing barrows.

• 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.

• Proceedings of the Korean Nutrition Society Conference
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• 1995.11b
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• pp.11-34
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• 1995

Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5741-5745
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• 2014

Purpose: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. Materials and Methods: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. Results: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment (p<0.05). Paclitaxel treatment caused cell cycle arrest and apoptosis via downregulating Bcl-2 expression. However, the effect could be abrogated by IGFBP-3 silencing. Conclusions: IGFBP-3 exhibits anti-apoptotic effects on paclitaxel-treated SGC-7901 cells via elevating Bcl-2 expression.

• Journal of Life Science
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• v.18 no.7
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• pp.931-939
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• 2008

The purpose of this study was to determine the effect of energy supplement on responses of plasma insulin-like growth factor (IGF)-1 and IGF binding proteins (IGFBPs) to growth hormone-releasing peptide-2 (GHRP-2) administration in normal protein-fed wethers, and to observe the effect of GHRP-2 treatment on hepatic growth hormone (GH) receptor in well-fed wethers. Plasma IGF-1 and 39-42 kDa IGFBP-3 during the HENP (CP, crude protein 0.34 and TDN, total digestible nutrients 1.83 kg/day DM, dry matter intake) treatment period were higher than in the LENP (CP 0.32 kg and TDN 0.87 kg/day DM intake) period (P<0.05). The response of GH was stimulated by GHRP-2 ($12.5\;{\mu}g/kg$ body weight/day) administration during both of the feed treatment periods (P<0.05). The area under curve (AUC) increment and average concentration of GH (0-180 min) with GHRP-2 administration was higher during HENP treatment than LENP treatment (P<0.01). During the HENP treatment period from day 1 to day 7 of twice daily GHRP-2 treatment, the plasma IGF-1 increment was increased on days 2, 6 and 7 of GHRP-2 administration (P<0.05). On the basis of ligand blotting, the proportions of plasma 39-43 kDa IGFBP-3 during the HENP treatment period only showed a significant difference on days 6 and 7 with GHRP-2 administration. No significant difference in the specific binding of $^{125}I-labeled$ oGH to hepatic membranes was detected between the saline and GHRP-2 treatments of the HENP-fed wethers. These results suggest that the nutritional balance between energy and protein may affect the endogenous GH / IGF-1 axis as well as plasma IGFBP-3 levels.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Clinical and Experimental Pediatrics
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• v.57 no.7
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• pp.310-316
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• 2014

Purpose: Prader-Willi syndrome (PWS) is a complex genetic disorder that results from the lack of paternally expressed genes in the chromosome 15q11-q13 region. This study was performed to delineate the clinical features of PWS infants and toddlers and the effects of two-year growth hormone (GH) treatment according to gender and age at the start of treatment. Methods: The clinical characteristics and the results of the GH treatment were reviewed retrospectively for 30 PWS patients diagnosed by molecular genetic testing and clinical manifestations. Results: The mean age at diagnosis with PWS was 13.7 months (2-47 months of age). All patients showed the characteristics of facial dysmorphism, including brown hair and almond-shaped eyes. Most patients showed developmental delays/mental retardation (93.3%), cryptorchidism (75%), feeding problems in infancy (73.3%), and neonatal or infantile hypotonia (66.7%). Among 30 patients, 14 PWS infants and toddlers had been treated with GH for more than two years. Two years of GH treatment resulted in an improvement in head circumference-standard deviation score (HC-SDS), body weight-SDS, insulin-like growth factor-1 (IGF-1) SDS, IGF binding protein-3 (IGFBP-3) SDS, lean body mass, and bone mineral content, especially in IGFBP-3 SDS and motor development in PWS patients younger than two years of age. There was significant increase in IGF-1 SDS and IGFBP-3 SDS among male PWS patients after GH treatment. Conclusion: Our study showed increases in IGFBP-3 SDS and an improvement in motor development among individuals under two years of age after GH treatment, and significant difference in IGF-1 SDS and IGFBP-3 SDS by gender.

• Archives of Plastic Surgery
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• v.32 no.6
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• pp.699-705
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• 2005

Transgender is the severe type of gender identity disorder. The prevalence rate of transgender is reported to occur to about 1 out of 50,000 men, and about 1 out of 10,000 women. As for Korea, it is estimated to have about 1400 transgender patients. Lately, not only the numbers of them are increasing but also they are influencing our society increasingly. As for female transgender patients, they take female hormone for a long term before and even after the operation to maintain their physical identity of female. We have analyzed insulin like growth factor-1(IGF-1), insulin like growth factor protein binding-3(IGFBP-3), female hormone, male hormone and thyroid hormone in female transgender patients who have undergone the gender reassignment operation. We examined the changes of hormone level due to having female hormone steadily, and also examined how the steady use of the hormone could affect body organs. As for IGF-1, it showed significantly low in the female transgender group compared to control ($319.30{\pm}37.4$ vs $539{\pm}55.0$, p<0.05). As for IGFBP-3, there was no significant difference ($2859{\pm}200.3$ vs $2607{\pm}262.5$, p>0.05). As for female hormone, there was no significant differences in FSH($13.42{\pm}13.8$ vs $8.95{\pm}3.5$, p>0.05), estradiol($104.41{\pm}97.1$ vs $121.68{\pm}60.2$, p>0.05), and LH($7.62{\pm}5.6$ vs $7.4{\pm}3.3$, p>0.05). Even in comparison of testosterone, there was no significant differences($0.23{\pm}0.09$ vs $0.33{\pm}1.33$, p>0.05). As for thyroid hormone, there was no significant differences in TSH and free T4($1.34{\pm}0.94$ vs $1.71{\pm}0.12$, $1.4{\pm}0.37$ vs $1.46{\pm}0.17$, p>0.05). Therefore, this study concludes that apart from the decreased level of IGF-1, the possible endocrine side-effect problem due to female hormone seems to be low because there was no differences of female, male, and thyroid hormone level compared with normal female. Further study will be required in metabolic change including bone metabolism occurred by decrease level of IGF-I.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.54-63
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• 2010

Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.