• 대한수의학회지
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• 제42권4호
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• pp.459-467
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• 2002

The sex steroid hormone progesterone is essential for normal development and maturation of the endometrium in preparation for the embryo implantation and the maintenance of pregnancy. Insulin-like growth factor (IGF) system that is composed of IGF-I, IGF-II, IGF binding proteins (IGFBPs) is also involved in the maintenance of pregnancy. In addition, liver, kidney, and uterus is a target tissue for IGF system. However, the effect of exogenous progesterone on IGF system was not elucidated in female rats. Therefore, we investigated the effect of progesterone on insulin-like growth factors (IGFs) and IGF-binding proteins in serum, liver, kidney, and uterus in female ovariectomized rats. IGFs concentration was measured by radioimmuoassay (RIA) and IGFBPs levels by western ligand blotting(WLB). IGF-I concentration was increased in serum, liver, and uterus, but not in kidney of progesterone-treated ovariectomized rats, compared to control (P<0.05). IGF-II concentration was decreased in liver, but not in serum, kidney, and uterus of progesterone-treated rats, compared to control (P<0.05). IGFBP-3 was increased in serum, but not in liver of progesterone-treated rats, compared to control. IGFBP-2 was decreased in kidney, but not in others tissues of progesterone-treated rats, compared to control. These results suggest that progesterone may exert diverse physiological functions via the tissue-specific regulation of IGFs/IGFBPs system in female rats.

• Asian-Australasian Journal of Animal Sciences
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• 제14권3호
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• pp.307-315
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• 2001

Litter size has been one of the important economic traits in porcine reproduction. The insulin-like growth factor (IGF) system has been shown to mediate actions of the steroid hormone or to synergize with other endocrine factors so that it consequently plays roles in reproductive processes, including ovulation, implantation, maintenance of pregnancy, and fetal development. However, the effect of the serum IGF system on porcine litter size has not been deeply studied. Therefore, this study was conducted to relate serum IFG-II concentration and IGF binding protein-3 (IGFBP-3) expression with porcine litter size. Moreover, the possible association of those with estrogen receptor (ER) as a candidate gene for litter size was investigated. Swine were separated into two groups showing high and low litter sizes, and sera were collected from sows in the estrous cycle to postnatal growth of their female progeny. Serum IFG-II concentration was measured by radioimmunoassay and IGFBP-3 expression was detected by Western ligand blotting. During the estrous cycle, IGFBP-3 expression in both groups decreased moderately from metestrus to estrus, but IFG-II concentration showed a reverse pattern. Also, IFG-II concentration and IGFBP-3 expression decreased gradually as pregnancy proceeded. Unlike IGFBP-3, IFG-II decreased moderately as newborn pigs grew. Significant differences in serum IFG-II amount between the two groups were detected at 60 (p<0.01), 75, 90, and 105 d (p<0.05) of pregnancy and at 60 (p<0.01), 45, and 105 d (p<0.05) of postnatal growth. Furthermore, based on ER genotypes, a high litter size group with genotypes AB and BB showed lower IFG-II concentration than a low litter size group with a genotype AA during pregnancy. Taken together, the results indicate that the serum IFG-II and IGFBP-3 are correlated with the litter size in pigs.

• 한국가축번식학회지
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• 제19권2호
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• pp.95-104
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• 1995

Mouse mammary epithelial cells(NMuMG) were maintained onto 6-well plates (3$\times$105 cells/well) or chambered slide (1$\times$104 cells/well), in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 hours, DMNB (1$\mu$M) was added and exposed to UV light (300nm, 3 second pulse) after 2 hours from DMNB addition in order to activate DMNB which induces a rapid transient increase in intracellular cAMP upon UV irradiation. EGF (100ng/ml) and/or IGF-I (10ng/ml) were treated at the time of UV irradiation. Nuclear labeling index was estimated as percent of nuclear labeled cells(percent of S phase of cells) by incorporation of 3H-thymidine into DNA(1 hour pulse with 1$\mu$Ci/ml). DMNB(1$\mu$M), EGF (100ng/ml) and/or IGF-I (10ng/ml) signifciantly increased nuclear labeling index than those of control (P<0.05). Addition of DMNB＋EGF or DMNB＋EGF＋IGF-I showed the interaction effect in nuclear labeling index (P<0.05). Protein kinase A activities by addition of EGF, IGF-I or EGF＋IGF-I were 10.5, 9.8 or 9.4 unit/mg protein, respectively, and no statistical difference was found in comparison with control (P>0.05). Additon of DMNB＋EGF showed the moderate interaction effect on tyrosyl kinase activity (P<0.1). In the fluorography analysis, there were no specific protein phosphorylation patterns were found at 1 or 15 minute by addition of DMNB. EGF and/or IGF-I. These results suggest that the interaction effect in nuclear labeling index by addition DMNB and EGF could be mediated through the modulation of tyrosyl kinase activity by cAMP.

• 한국식품영양과학회지
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• 제32권3호
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• pp.437-443
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• 2003

선행연구에서 라이코펜이 HT-29세포의 증식을 억제하는 것을 관찰하였기 때문에 본 연구는 그 기전을 연구하기 위하여 수행되 었다. 라이코펜이 HT-29 세포의 사멸을 유도하는지 조사하기 위해서 여러 농도의 라이코펜이 포함된 배지에서 세포를 4일 동안 배양하였다. 라이코펜 농도의 증가에 따라 사멸되는 세포에서 나타나는 특징의 하나인 DNA fragmentation이 증가하는 것을 관찰하였다. Western blot을 수행하여 얻은 결과에 의하면 라이코펜이 IGF-IR, IRS-1, PI3K, Akt와 같은 IGF-IR pathway에 속하는 단백질의 수준을 감소시켰다. IGF-IR의 인산화를 유도하기 위해서 라이코펜이 포함된 배지에서 세포를 배양하고 IGF-I을 첨가하여 0, 5, 10, 60분간 배양한 다음 IGF-IR antibody를 이용하여 immunoprecipitation을 수행하였다. 라이코펜은 IGF-I에 의한 IGF-IR, IRS-1의 인산화와 IGF-IR와 PI3K의 결합을 감소하고 인산화된 Akt를 감소시켰다. 이와 같은 IGF-IR signaling의 억제는 이 대장암세포에 존재하는 IGF-II의 autocrine loop을 억제하는 원인이 될 수 있어, 라이코펜의 암세포증식을 억제하는 기전 중의 하나가 될 수 있다. 라이코펜은 토마토와 그 가공품에 많이 존재하는 물질로 자연적인 식사를 통해 많이 섭취할 수 있는 물질이다. 라이코펜의 항암 기전을 밝혀냄으로써 미래 암예방과 치료를 위한 중요한 기능성 영양소를 생산할 수 있는 기초를 마련해줄 수 있을 것으로 기대된다.

• 한국수정란이식학회지
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• 제12권3호
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• pp.229-246
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• 1997

Implantation is a most important biological process during pregnancy whereby conceptus establishes its survival as well as maintenance of pregnancy. During the periimplantation period, both uterine endometriurn and conceptus synthesize and secrete a host of growth factors and cytokines which mediate the actions of estrogen and /or progesterone and also exert their steroid-independent actions. Growth factors expressed by the materno-conceptal unit en masse have important roles in cell migration, stimulation or inhibition of cell proliferation, cellular differentiation, maintenance of pregnancy and materno-conceptal communications in an autorcrine /paracrine manner. The present review focuses on the role of the intrauterine IGF system during periimplantation conceptus development. The IGF system comprises of IGF- I and IGF- II ligands, types I and II IGF receptors and six or more IGF-binding proteins(IGFBPs). IGFs and IGFBPs are expressed and secreted by uterine endometrium with tissue, pregnancy stage and species specificities under the influence of estrogen, progesterone and other growth factor(s). Conceptus also synthesizes components of the IGF system beginning from a period between 2-cell and blastocyst stages. Maternal IGFs are utilized by both maternal and conceptal tissues; conceptus-derived growth factors are believed to be taken up primarily by conceptus. IGFs enhance the development of both maternal and conceptal compartments in a wide range of biological processes. They stimulate proliferation and differentiation of endometrial cells and placental precursor cells including decidual transformation from stromal cells, placental formation and the synthesis of some steroid and protein hormones by differentiated endometrial cells or placenta. It is also well-documented in a number of experimental settings that both IGFs stimulate preimplantation embryo development. In slight contrast to these, prenatal mice carrying a null mutation of IGF and /or IGF receptor gene do not exhibit any apparent growth retardation until after implantation. Reason (s) for this discrepancy between the knock-out result and the in vitro ones, however, is not known. IGFBPs, in general, are believed to inhibit IGF action within the materno-conceptal unit, thereby allowing endometrial stromal cell differentiation as well as dampening ex cessive placental invasion into maternal tissue. There is evidence, however, indicating that IGFBP can enhance IGF action depending on environrnental conditions perhaps by directioning IGF ligand to the target cell. There is also a third possibility that certain IGFBPs and their proteolytic fragments may have their own biological activities independent of the IGF. In addition to IGFBPs, IGFBP proteases including those found within the uterine tissue or lumen are thought to enhance IGF bioavailability by degrading their substrates without affecting their bound ligand. In this regard, preliminary results in early pregnant pigs suggest that a partially characterized IGFBP protease activity in uterine luminal fluid enhances intrauterine IGF bioavailability during conceptus morphological development. In summary, a number of in vitro results indicate that IGFs stimulates the development of the rnaterno-conceptal unit during the periimplantation period. IGFBPs appear to inhibit IGF action by sequestering their ligands, whereas IGFBP proteases are thought to enhance intrauterine bioavailability of IGFs. Much is remaining to be clarified, however, regarding the roles of the individual IGF system components. These include in vivo evidence for the role of IGFs in early conceptus development, identification of IGF-regulated genes and their functions, specific roles for individual IGFBPs, identification and characterization of IGFBP proteases. The intrauterine IGF club house thus will be paying a lot of attention to forthcoming results in above and other areas, with its door wide-open!

• Asian-Australasian Journal of Animal Sciences
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• 제23권3호
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• pp.366-371
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• 2010

Twelve Suffolk${\times}$Small-tail-Han male sheep (body weight 21-26 kg), aged four months, were used to study the effects of volatile fatty acids (VFA) on IGF-I (insulin-like growth factor-I), IGFBP-3 (insulin-like growth factor binding protein-3), GH (growth hormone), insulin and glucagon in plasma, and IGF-I and IGFBP-3 in different tissues. The sheep were randomly divided into four groups with 3 sheep in each group. The sheep were sustained by total intragastric infusions and four levels of mixed VFA (the molar proportion of acetic acid, propionic acid and butyric acid was 65:25:10), which supplied 333, 378, 423 and 468 KJ energy/kg $W^{0.75}$/d, were infused into the rumen as experimental Treatments I, II, III and IV, respectively. The experiment lasted 12 days, of which the first 8 days were for pretreatment and the last 4 days for collection of samples. At the end of the experiment, blood samples were taken and then the sheep were slaughtered and tissue samples from the rumen ventral sac, rumen dorsal sac, liver, duodenum and Longissimus dorsi muscle were obtained. IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in different tissues were analysed. Results showed that the concentration of IGF-I, IGFBP-3, GH, insulin or glucagon in plasma and the content of IGF-I and IGFBP-3 in the rumen dorsal sac, rumen ventral sac, liver or Longissimus dorsi muscle were increased with VFA infusion level (p<0.05). No significant differences were found in duodenum IGF-I between Treatments I and II and in rumen dorsal sac IGFBP-3 between Treatments II and III (p>0.05). It was concluded that IGF-I, IGFBP-3, GH, insulin and glucagon in plasma and IGF-I and IGFBP-3 in rumen dorsal sac, rumen ventral sac, liver and Longissimus dorsi muscle were increased significantly with increasing level of ruminal infusion of mixed VFA.

• 대한의생명과학회지
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• 제12권3호
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• pp.217-224
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• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Journal of Nutrition and Health
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• 제35권2호
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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.

• Asian-Australasian Journal of Animal Sciences
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• 제21권5호
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• pp.754-768
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• 2008

The past decades have seen enormous advances in our understanding of how GH acts. GH is a pituitary-derived polypeptide hormone that has diverse physiological effects including the regulation of bone growth, carbohydrate and lipid metabolism. The effects of GH are mediated directly and indirectly through IGF-I. In addition, GH stimulates the hepatic production of ALS. In postnatal life, IGF-I and -II circulate as 150 kDa ternary complexes consisting of one molecule each of IGFBP-3 or IGFBP-5, IGF-I or IGF-II and ALS. It is now known that ALS increases significantly the half-lives of the IGFs, IGFBP-3 and -5, and therefore is responsible for maintaining a circulating reservoir for each of these proteins.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2005년도 창립 30주년 및 춘계학술대회
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• pp.47-54
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• 2005

수퇘지에서는 타 종의 수컷에서와는 달리 성선호르몬이 자발적인 사료섭취를 억제하다. 따라서 거세 돼지는 수퇘지나 암퇘지에 비해 사료섭취량이 과다하여 과비해지는 경향이 있다. 본 연구에서는 교잡종 거세비육돈에서 Revalor H[실험 I; 140mg trenbklone acetate(합성 androgen) + 14mg estradiol-$17\beta(E_{2}\beta)$] 및 Compudose[실험 II; 24mg $E_{2}\beta$]를 implantation 했을 때 성장효율, 도체특성 및 혈중 IGH-I 및 IGF-binding protein-3(IGFBP-3) 농도에 미치는 영향을 조사하고자 2회의 사양실헝(I & II)를 수행하였다. 실험 I에서는 생체중 약60kg의 교잡종 거세비육돈 64두를 8돈방에 완전임의배치하여 2[implant; 처리 대비 무처리] $\times$ 2[사양; 무제한급여 대비 $80\%$ 무제한급여] $\times$ 2[사료; 대조(NRC 권장 수준의 $103\%$) 대비 저에너지($87\%$ NRC 권장량) 사료] 'factorial' 사양시험을 수행하였고, 실험 II에서는 80두의 거세비육돈(10두/돈방)을 이용하여 implant의 효과 유무를 조사하였다. 실험 I과 II에서 모든 공시돈은 생체중 $100\~110kg$ 시 도축되었다. Revalor H와 Compudose implant 제제는 공히 사료섭취량과 등지방두께를 저하시키고, 도체의 주요 이화학적 특성에는 영향을 미치지 않고 혈중 IGF-I 농도를 증가시켰다. 또한 이들 측정항목에서 Revalor H implant는 제한사양, 저에너지 사료, 혹은 Compudose 이상의 효과를 나타내었고, 증체를 억제하였으나 사료효율은 증진시켰으며, 후자(사양, 사료)와의 상호작용은 나타나지 않았다. 이상의 결과는 거세비육돈에서 1) androgen과 estrogen은 공히 자발적인 사료섭취와 등지방 침적을 억제하고 IGF-I 분비를 증가시키며, 2) 성선스테로이드호르몬의 이 같은 성장에 미치는 효과의 일부는 IGF-I을 통해 매개될 수도 있을을 시사한다.