• Clinical and Experimental Reproductive Medicine
• /
• v.43 no.2
• /
• pp.97-101
• /
• 2016

Objective: Growth hormone and its mediator, insulin-like growth factor-1 (IGF-1), have been suggested to exert gonadotropic actions in both humans and animals. The present study was conducted to assess the relationship between serum IGF-1 concentration, seminal plasma concentration, and sperm parameter abnormalities. Methods: A total of 79 men were enrolled in this study from December 2011 to July 2012 and were prospectively analyzed. Patient parameters analyzed included age, body mass index, smoking status, urological history, and fertility history. Patients were divided into four groups based on their semen parameters: normal (A, n=31), abnormal sperm motility (B, n=12), abnormal sperm morphology (C, n=20), and two or more abnormal parameters (D, n=16). Patient seminal plasma and serum IGF-1 concentrations were determined. Results: Patient baseline characteristics were not significantly different between any of the groups. The serum IGF-1 levels in groups B, C, and D were significantly lower than the levels in group A; however, the seminal plasma IGF-1 levels were not significantly different between any of the groups. Conclusion: Men with abnormal sperm parameters had significantly lower levels of serum IGF-1 compared with men with normal sperm parameters. Seminal plasma IGF-1 levels, however, did not differ significantly between the groups investigated here. Further investigations will be required to determine the exact mechanisms by which growth hormone and IGF-1 affect sperm quality.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.5
• /
• pp.618-628
• /
• 1999

Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.

• BMB Reports
• /
• v.33 no.6
• /
• pp.454-462
• /
• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• Clinical and Experimental Pediatrics
• /
• v.48 no.3
• /
• pp.298-305
• /
• 2005

Purpose : We performed this study to evaluate the mean serum levels of insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein(IGFBP)-2 and IGFBP-3 in healthy Korean children according to age and sex. Methods : Ninety two healthy children, consisting of 42 boys and 50 girls, were classified into five groups according to age : neonate; infancy; early childhood; late childhood; and adolescence. We measured serum levels of IGF-I, IGFBP-2 and IGFBP-3 by enzyme-linked immunosorbent assay(ELISA) and analysed the serum levels according to sex and age group. Results : For boys, the mean serum levels of IGF-I(ng/mL) in neonate, infancy, early childhood, late childhood and adolescence were $41.1{\pm}3.6$, $70.9{\pm}33.7$, $103.5{\pm}97.2$, $89.8{\pm}46.5$ and $51.4{\pm}27.8$, respectively. Those of IGFBP-2(ng/mL) were $8.2{\pm}3.4$, $5.8{\pm}0.4$, $9.3{\pm}4.0$, $9.5{\pm}1.1$ and $7.0{\pm}0.5$, respectively. Those of IGFBP-3(ng/mL) were $559.2{\pm}215.2$, $1,333.3{\pm}692.5$, $2,254.6{\pm}1,513.8$, $2,447.1{\pm}1,464.2$, $1,533.6{\pm}807.4$, respectively. For girls, the mean serum levels of IGF-I(ng/mL) according to five age groups were $53.3{\pm}9.5$, $99.3{\pm}45.8$, $69.6{\pm}51.1$, $106.2{\pm}67.0$ and $145.1{\pm}127.8$, respectively. Those of IGFBP-2 (ng/mL) were $9.1{\pm}7.4$, $5.3{\pm}0.9$, $6.9{\pm}2.0$, $10.5{\pm}3.0$ and $7.9{\pm}1.3$, respectively. Those of IGFBP-3(ng/mL) were $858.2{\pm}433.4$, $1,834.8{\pm}851.3$, $1,404.3{\pm}570.2$, $2,203.5{\pm}899.4$ and $2,029.3{\pm}1,316.7$, respectively. There were significant positive correlations observed between IGF-I and IGFBP-3 levels(r=0.589, P=0.000). Conclusion : IGF-I and IGFBP-3 levels increased as children get older. The peak level of IGFBP-3 was observed in late childhood for both boys and girls, suggesting a current trend of children reaching peak growth velocity before adolescence. The IGFBP-2 level was higher in neonates compare to infancy, suggesting that IGFBP-2 is an important substance for fetal growth.

• Journal of Life Science
• /
• v.24 no.12
• /
• pp.1284-1290
• /
• 2014

Fatty acid transporter protein 1 (FATP1) is highly expressed in skeletal muscle and modulates fatty acid uptake and metabolism. However, the influence of insulin-like growth factor-I (IGF-I), a master regulator of skeletal muscle cells, on FATP1 in skeletal muscle cells has not been demonstrated. To investigate the effect of IGF-I on FATP1 and the expression of the IGFBP5 protein, differentiated C2C12 murine skeletal muscle cells were treated with 20 ng/ml of IGF-I at different time points. The results showed that IGF-I increased FATP1 and IGFBP5 protein expression in a time-dependent manner. To determine whether this induction of FATP1 by the IGF-I treatment was regulated pretranslationally, the mRNA level of FATP1 was measured by real-time quantitative PCR. The IGF-I treatment resulted in very rapid induction of the FATP1 mRNA transcript in C2C12 myotubes. FATP1 mRNA increased 169% and 132% after 24 and 48 h of the IGF-I treatment, respectively, and it returned to control levels after 72 h of the treatment, suggesting that the FATP1 gene is regulated pretranslationally by IGF-I in skeletal muscle cells. This is the first evidence that IGF-I can regulate the expression of FATP1. In conclusion, IGF-I induced rapid transcriptional modification of the FATP1 gene in C2C12 skeletal muscle cells and had modulating effects on fatty acid uptake proteins and oxidative proteins.

• Development and Reproduction
• /
• v.25 no.1
• /
• pp.67-72
• /
• 2021

This study investigated the IGF-1 signal in specific tissues using Pacific oysters artificially matured via water temperature elevation. Pacific oysters were subjected to water temperature elevation from March to June, and 20 were randomly sampled each month. The condition index (CI) and tissue weight rate (TWR) were examined by measuring shell length, shell height, shell width, and soft tissue weight. The IGF-1 signal in tissues (adductor muscle, digestive glands, gills, labial palps, mantle edges, and gonads) was analyzed by sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. From April to June, the TWR of females and males increased from 19.1±2.9 to 21.0±3.6 and 18.2±2.0 to 19.2±2.5, respectively, while the CI remained the same. The IGF-1 signal in each tissue differed. IGF-1 was expressed in the adductor muscle, while tyrosine was expressed in all tissues. The phosphor (p)-ERK and p-AKT activities were high in the adductor muscle, mantle edge, and gonads. IGF-1 signaling affected the growth and maturity of the Pacific oysters examined.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.29 no.3
• /
• pp.493-499
• /
• 2000

골감소증 환자의 혈청중에 존재하는 IGFBP-5의 존재와 변화를 검토한 결과, 골감소즈 환자에서는 정상 대조군에 비해 IGFBP-5가 감소하였는데 이 변화는 IGFBP-5의 분해효소가 작용하기 때문인 것으로 나타났다. IGFBP-5에 작용하는 단백질분해효소 저해제중 metallo계인 EDTA 및 1,10-phenanthroline과 seriner계인 aprotinin, heparin, heparin cofactor 2(HC2), heparine+HC2가 IGFBP-5에 대해 저해효과가 크므로 metalloprotease이면서 serine protease의 성질을 가지는 효소들이 IGFBP-5에 작용하였다. IGF-I과 IGF-II 그리고 insulin은 효소 활성에 아무런 영향이 없었다. IGFBP-5의 zymography에서 정상인과 골감소증 환제어서 180 kDa 크기의 band가 나타났고, gelatin zymography에서 정상 대조군의 경우 66 kDa과 97 kDa 정도의 band가 확인되었고 골감소증 환자의 경우는 69 kDa의 band가 확인되었다.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.26 no.2
• /
• pp.285-290
• /
• 1997

The insulin-like growth factors(IGFs) are bound to several binding proteins(IGFBPs) that appear to regulate IGF transport, receptor binding, and its action. The concentration of these peptides are altered by catabolic conditions. To determine IGF-I and IGFBP levels in noninsulin-dependent diabetes mellitus (NIDDM), sera was obtained from 5 patients and 7 controls. Serum levels of IGF-I in NIDDM were lower than those in either of the controls. By western immunoblot analysis, especially IGFBP-1 levels are increased, whereas IGFBP-3 levels decreased and their fragments was increased in NIDDM serum. IGFBP-3 proteolytic activity in NIDDM sera was inhibited by phenylmethylsulfonylfluoride (PMSF), aprotinin, and ethylenediaminetetraacetic acid(EDTA). This pattern of inhibition was consistent with a metal-dependent serine protease. By gelatin zymography, these proteolytic enzymes were identified as the size of 97 and 69 kDa. IGFBP-1, which is primarily insulin regulated, was increased in NIDDM and may modulate circulating IGF-I levels by regulating capillary passage of IGF-I. IGFBP-3 proteolysis markedly reduces its affinity for the IGFs, particularly for IGF-I. This accelerates their kinetics of dissociation, thereby increasing the proportions of IGF-I in free form and its availability to the cells.

• Childhood Kidney Diseases
• /
• v.3 no.2
• /
• pp.109-116
• /
• 1999

Purpose: Insulin-like growth factor(IGF)-I and -II are peptide growth factor whose activity is modulated by interaction with the family of six IGF-binding proteins(IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. This study was designed to examine temporal expression of IGFBPs in kidney during renal development and postischemic regeneration in rat. Method: The expression of IGFBPs in kidney during renal development from 15th day of gestation to adult life by using Northern blot analysis. We also examined the renal IGF-IGFBP axis in uremic rat by using Northern blot and immunohistochemistry. Results: The mRNA of IGFBP-1 and -3 were not or barely detected in fetal stages. However, the mRNA level of IGFBP-1 and -3 were increased gradually from day 7 after birth to adult. In contrast, the mRNA of IGFBP-2 and -5 were highly expressed in fetal stages and maintained almost same levels until day 7 (IGFBP-2) or day 30 (IGFBP-5) after birth, then their levels decreased markedly. The mRNA of IGFBP-4 were expressed moderately in fetal kidney and increased gradually after birth. Interestingly, the mRNA of IGFBP-1 and-4 were induced up to 3-5 fold during maximum regeneration period and were recovered to normal levels after acute ischemic injury. In contrast, the mRNA level of IGFBP-3 and-IGFBPrP-1 were decreased slightly at 1 day after ischemic injury, then recovered to normal level during maximum regeneration period. Conclusion: There were differential expressions of IGFBPs in kidney that can modulate IGF action on developing, differentiating, maintaining, and regenerating renal structure and function.

• Advances in pediatric surgery
• /
• v.3 no.2
• /
• pp.98-107
• /
• 1997

To determine whether bile juice exclusion can prevent the mucosal damage, and Insulin-like growth factor-I can promote mucosal regeneration in ischemia-reperfusion injury of the bowel, 39 weanling rats with 10 cm of Thiry-Vella loop were studied. Animal groups were; Control, BL(common bile duct ligation), IGF{insulin-like growth factor-I(IGF-I) infusion} and IGF-BL(combined treatment). IGF-I(1.5 mg/kg/day) was continuously delivered through a subcutaneously implanted miniosmotic pump. After 15 minutes of superior mesenteric artery clamping, a tissue specimen(P) was taken after 30 minutes of reperfusion. Intestinal continuity was restored to allow oral feeding. A specimen of main tract(M) and another of the Thiry-Vella loop(T) were collected for histomorphometry after 48 hours of reperfusion and free feeding. Villus size ratio(VSR), crypt depth(CD), crypt-depth/villus-height ratio(CVR) and injury score(IS) were measured in 15 consecutive villi. The postoperative mortalities of bile duct ligation groups(BL and IGF-BL) were higher than those of other groups. In control group, VSR of M was lower(P<0.05) than P or T, but not in the other groups. VSR of M in control was lower than those in other groups. CD of T in control, IGF and IGF-BL group were higher than those of M. CD of M and T showed gradual increments from control, IGF and IGF-BL group, respectively. CVR of M and T in IGF group were higher than those in control. CVR in IGF-BL group, T was higher than M, and M was higher than P. About IS, M of BL($20.1{\pm}2.5$) and IGF-BL($20.9{\pm}3.3$) groups were significantly lower than that of control($32.4{\pm}2.5$). These results suggest that the exclusion of bile juice reduces the severity of the reperfusion injury of the mucosa, by inability to activate pancreatic enzymes and IGF-I stimulates mucosal regeneration in injured bowel, and the effect is potentiated by bile juice exclusion.