Typescript (Photocopy) Includes papers co-authored by author. Includes bibliographies.

Thesis (Ph. D.)--Dept. of Biochemistry, University of Adelaide, 1990. / Typescript (Photocopy). Includes papers co-authored by author. Includes bibliographical references.

Appropriate placental development in early gestation is essential for subsequent placental function and hence optimal fetal growth and pregnancy outcome. Placental insufficiency has been implicated in common disorders of pregnancy, which result in fetal and maternal mortality or morbidity, and also increase the risk of poor health in adult offspring. Prior to the onset of maternal blood flow to the placenta at ~10 weeks of gestation, placentation occurs in a relatively hypoxic environment, which is essential for healthy pregnancy. IGF-II is abundantly expressed by the invasive trophoblast and may interact with oxygen to regulate placentation. Additionally, maternally-derived IGFs may act on the placenta and the mother to regulate fetal growth. This thesis investigated the role and interaction of oxygen and IGF-II on human placental outgrowth during early pregnancy in vitro. Furthermore, the impact of maternal IGF treatment during early to mid pregnancy, on placental development and substrate transfer, nutrient partitioning between the mother and fetus, and fetal growth, were also determined in mid and late gestation in guinea pigs. We have demonstrated, using human early first trimester placental villous explants, that IGF-II mediates the effect of hypoxia on placental outgrowth. Culture of placental explants in hypoxia, or with exogenous IGF-II, enhanced trophoblast outgrowth and inhibited TGF-β1 activation, a negative regulator of trophoblast function. In addition, culture of explants in hypoxia induced Igf2 gene expression in outgrowing trophoblast, without altering Upar, Igf1r, Igf2r or Tgfβ1 transcription. We propose that this novel interaction of oxygen, IGF-II and TGF-β1 during pregnancy is an important determinant of placental development. Furthermore, we showed that exogenous IGF-II stimulates villous explant trophoblast outgrowth in placenta from >10 weeks gestation, suggesting that IGF-II may be a potential therapeutic agent to enhance placental growth. In guinea pigs, maternal treatment with IGF-I or IGF-II, in early to mid pregnancy, has sustained anabolic effects on fetal growth, enhanced fetal survival and increased placental delivery, and fetal and maternal utilization of, glucose and amino acids near term. These effects were also evident by mid gestation following earlier IGF-I treatment. Despite these similar pregnancy outcomes, there were IGF specific effects on the placenta and mother, suggesting that IGFs may mediate some of their effects via different pathways. IGF-I administration severely reduced maternal adiposity in late pregnancy, elicited its effects by substantially improving development of the placental exchange region, which correlated with placental function. We have suggested that the discrete effects of IGF-I and IGF-II stem from distinct interactions of the IGFs with various receptors. Maternal administration of an analogue of IGF-II that selectively interacts with IGF2R (Leu ²⁷-IGF-II), revealed that many of the effects of IGF-II treatment, were mediated by IGF2R, while IGF-I presumably acts through IGF1R. Together, this work has highlighted the major and somewhat complementary roles of maternal IGFs during the first half of pregnancy, in regulating placental development, fetal growth and pregnancy success. Importantly, it indicates the potential use of maternal IGFs in diagnostic and therapeutic approaches to pregnancy complications. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277715 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2007.

Appropriate placental development in early gestation is essential for subsequent placental function and hence optimal fetal growth and pregnancy outcome. Placental insufficiency has been implicated in common disorders of pregnancy, which result in fetal and maternal mortality or morbidity, and also increase the risk of poor health in adult offspring. Prior to the onset of maternal blood flow to the placenta at ~10 weeks of gestation, placentation occurs in a relatively hypoxic environment, which is essential for healthy pregnancy. IGF-II is abundantly expressed by the invasive trophoblast and may interact with oxygen to regulate placentation. Additionally, maternally-derived IGFs may act on the placenta and the mother to regulate fetal growth. This thesis investigated the role and interaction of oxygen and IGF-II on human placental outgrowth during early pregnancy in vitro. Furthermore, the impact of maternal IGF treatment during early to mid pregnancy, on placental development and substrate transfer, nutrient partitioning between the mother and fetus, and fetal growth, were also determined in mid and late gestation in guinea pigs. We have demonstrated, using human early first trimester placental villous explants, that IGF-II mediates the effect of hypoxia on placental outgrowth. Culture of placental explants in hypoxia, or with exogenous IGF-II, enhanced trophoblast outgrowth and inhibited TGF-β1 activation, a negative regulator of trophoblast function. In addition, culture of explants in hypoxia induced Igf2 gene expression in outgrowing trophoblast, without altering Upar, Igf1r, Igf2r or Tgfβ1 transcription. We propose that this novel interaction of oxygen, IGF-II and TGF-β1 during pregnancy is an important determinant of placental development. Furthermore, we showed that exogenous IGF-II stimulates villous explant trophoblast outgrowth in placenta from >10 weeks gestation, suggesting that IGF-II may be a potential therapeutic agent to enhance placental growth. In guinea pigs, maternal treatment with IGF-I or IGF-II, in early to mid pregnancy, has sustained anabolic effects on fetal growth, enhanced fetal survival and increased placental delivery, and fetal and maternal utilization of, glucose and amino acids near term. These effects were also evident by mid gestation following earlier IGF-I treatment. Despite these similar pregnancy outcomes, there were IGF specific effects on the placenta and mother, suggesting that IGFs may mediate some of their effects via different pathways. IGF-I administration severely reduced maternal adiposity in late pregnancy, elicited its effects by substantially improving development of the placental exchange region, which correlated with placental function. We have suggested that the discrete effects of IGF-I and IGF-II stem from distinct interactions of the IGFs with various receptors. Maternal administration of an analogue of IGF-II that selectively interacts with IGF2R (Leu ²⁷-IGF-II), revealed that many of the effects of IGF-II treatment, were mediated by IGF2R, while IGF-I presumably acts through IGF1R. Together, this work has highlighted the major and somewhat complementary roles of maternal IGFs during the first half of pregnancy, in regulating placental development, fetal growth and pregnancy success. Importantly, it indicates the potential use of maternal IGFs in diagnostic and therapeutic approaches to pregnancy complications. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277715 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2007.

Appropriate placental development in early gestation is essential for subsequent placental function and hence optimal fetal growth and pregnancy outcome. Placental insufficiency has been implicated in common disorders of pregnancy, which result in fetal and maternal mortality or morbidity, and also increase the risk of poor health in adult offspring. Prior to the onset of maternal blood flow to the placenta at ~10 weeks of gestation, placentation occurs in a relatively hypoxic environment, which is essential for healthy pregnancy. IGF-II is abundantly expressed by the invasive trophoblast and may interact with oxygen to regulate placentation. Additionally, maternally-derived IGFs may act on the placenta and the mother to regulate fetal growth. This thesis investigated the role and interaction of oxygen and IGF-II on human placental outgrowth during early pregnancy in vitro. Furthermore, the impact of maternal IGF treatment during early to mid pregnancy, on placental development and substrate transfer, nutrient partitioning between the mother and fetus, and fetal growth, were also determined in mid and late gestation in guinea pigs. We have demonstrated, using human early first trimester placental villous explants, that IGF-II mediates the effect of hypoxia on placental outgrowth. Culture of placental explants in hypoxia, or with exogenous IGF-II, enhanced trophoblast outgrowth and inhibited TGF-β1 activation, a negative regulator of trophoblast function. In addition, culture of explants in hypoxia induced Igf2 gene expression in outgrowing trophoblast, without altering Upar, Igf1r, Igf2r or Tgfβ1 transcription. We propose that this novel interaction of oxygen, IGF-II and TGF-β1 during pregnancy is an important determinant of placental development. Furthermore, we showed that exogenous IGF-II stimulates villous explant trophoblast outgrowth in placenta from >10 weeks gestation, suggesting that IGF-II may be a potential therapeutic agent to enhance placental growth. In guinea pigs, maternal treatment with IGF-I or IGF-II, in early to mid pregnancy, has sustained anabolic effects on fetal growth, enhanced fetal survival and increased placental delivery, and fetal and maternal utilization of, glucose and amino acids near term. These effects were also evident by mid gestation following earlier IGF-I treatment. Despite these similar pregnancy outcomes, there were IGF specific effects on the placenta and mother, suggesting that IGFs may mediate some of their effects via different pathways. IGF-I administration severely reduced maternal adiposity in late pregnancy, elicited its effects by substantially improving development of the placental exchange region, which correlated with placental function. We have suggested that the discrete effects of IGF-I and IGF-II stem from distinct interactions of the IGFs with various receptors. Maternal administration of an analogue of IGF-II that selectively interacts with IGF2R (Leu ²⁷-IGF-II), revealed that many of the effects of IGF-II treatment, were mediated by IGF2R, while IGF-I presumably acts through IGF1R. Together, this work has highlighted the major and somewhat complementary roles of maternal IGFs during the first half of pregnancy, in regulating placental development, fetal growth and pregnancy success. Importantly, it indicates the potential use of maternal IGFs in diagnostic and therapeutic approaches to pregnancy complications. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277715 / Thesis (Ph.D.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2007.

Thesis (M.S. in genetics and cell biology)--Washington State University, May 2009. / Title from PDF title page (viewed on Apr. 5, 2010). "School of Molecular Biosciences." Includes bibliographical references (p. 39-45).

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Primary cultures of skeletal muscle satellite cells were induced to proliferate by exposure to physiologic levels of somatomedins and pharmacologic levels of insulin. Dexamethasone inclusion in serum containing medium facilitated the ovine somatomedin (oSm) (P < 0.05), but that both were different than the proliferation induced by MSA/rIGF-II (P < 0.05). In the presence of insulin concentrations that promote maximum proliferation, addition of oSm did not produce an additive effect, whereas the addition of MSA/rIGF-II did produce a significant increase in satellite cell proliferation above that induced by insulin. A more, in depth, analysis of the interaction of MSA/rIGF-II with its satellite cell receptor under a variety of experimental conditions revealed that binding of ¹²⁵I-MSA/rIGF-II was inhibited by oSm and MSA/rIGF-II, but not by insulin. Migration, and localization of ¹²⁵I-MSA/rIGF-II-receptor complexes in 7% sodium dodecyl sulfate polyacrylamide gels suggest that these complexes are Type II IGF receptors. In addition, this receptor system of satellite cells was shown to be modulated by other hormones; notably, pre-exposure of cells with insulin increased ¹²⁵I-MSA/rIGF-II binding, while oSm, or MSA/rIGF-II preincubation decreased the binding of ¹²⁵I-MSA/rIGF-II. Therefore, the proliferative effects of MSA/rIGF-II appeared not as a consequence of MSA/rIGF-II induction of other receptor types such as the insulin, or Type I IGF receptor systems. Concommitant to the previous experimentation, oSm was further examined in an initial attempt to elucidate its biologic binding mechanism in myogenic satellite cells. Binding of ¹²⁵I-oSm was inhibited by MSA/rIGF-II, insulin and IGF-I; thus these data suggest that oSm may be the ovine analog to human IGF-I. In addition, pre-exposure of cells to MSA/rIGF-II and oSm down-regulated the ability of satellite cells to bind oSm, while only concentrations of insulin greater than 550 ng insulin had this ability. Collectively, these data support the hypothesis that somatomedins play an important role in the control of postnatal muscle growth by providing a link between these hormones and satellite cells, one of the significant target cells involved in the growth process.

by Yu Wai Fu, Jason. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1997. / Includes bibliographical references (leaves 112-120). / ACKNOWLEDGMENTS --- p.i / ABSTRACT --- p.ii / TABLE OF CONTENTS --- p.iii / Chapter CHAPTER 1 --- INTORDUCTION --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Historical Overview --- p.3 / Chapter 1.2.1 --- Insulin-Like Growth Factors I and II --- p.3 / Chapter 1.2.2 --- IGF Receptors --- p.5 / Chapter 1.2.3 --- IGF Binding Proteins --- p.7 / Chapter 1.3 --- Origin and Production of IGFs --- p.7 / Chapter 1.3.1 --- The Hypothalamo-Pituitary-GH-IGF-I Axis --- p.7 / Chapter 1.3.2 --- Factors Regulating IGF production --- p.9 / Chapter 1.3.3 --- Expression of IGFs in the Central Nervous System --- p.11 / Chapter 1.4 --- Actions of IGFs --- p.12 / Chapter 1.4.1 --- Insulin-like Metabolic Effects --- p.12 / Chapter 1.4.2 --- Mitogenic Effects --- p.13 / Chapter 1.4.3 --- Effects on Differentiation --- p.13 / Chapter 1.4.4 --- IGFs in Reproductive System --- p.14 / Chapter 1.4.5 --- IGF Actions in the Central Nervous System --- p.14 / Chapter 1.5 --- Transgenic and Knockout Animal Models for IGFs --- p.15 / Chapter 1.6 --- Molecular Biology of IGFs --- p.17 / Chapter 1.6.1 --- Structure of the IGF Genes --- p.17 / Chapter 1.6.2 --- Expression of IGF Genes --- p.21 / Chapter 1.6.3 --- Regulation of IGF Gene Expression --- p.23 / Chapter 1.7 --- IGF Receptors --- p.24 / Chapter 1.7.1 --- IGF-I Receptor --- p.24 / Chapter 1.7.2 --- IGF-II Receptor --- p.26 / Chapter 1.8 --- IGFBPs --- p.26 / Chapter 1.9 --- Teleost IGFs --- p.28 / Chapter 1.9.1 --- The GH-IGF-Axis in Teleost --- p.28 / Chapter 1.9.2 --- Osmoregulation and Other Biological Actions of IGFin Teleost --- p.29 / Chapter 1.9.3 --- Molecular Biology of IGFs in Teleost --- p.30 / Chapter 1.9.4 --- IGFBPs and IGF Receptors in Teleost --- p.31 / Chapter 1.10 --- Rationale and Aim of the Present Study --- p.32 / Chapter CHAPTER 2 --- SEARCH OF IGF-I PROMOTER BY GENOMIC DNA POLYMERASE CHAIN REACTION --- p.34 / Chapter 2.1 --- Introduction --- p.34 / Chapter 2.2 --- Materials --- p.35 / Chapter 2.3 --- Methods --- p.39 / Chapter 2.3.1 --- Preparation of Genomic DNA from Carp Testis --- p.39 / Chapter 2.3.2 --- Restriction Enzyme Digestion of Genomic DNA --- p.40 / Chapter 2.3.3 --- Polymerase Chain Reaction --- p.40 / Chapter 2.3.3.1 --- Ligation of the Cassette to Digested Genomic DNA --- p.40 / Chapter 2.3.3.2 --- Amplification by PCR --- p.40 / Chapter 2.3.4 --- Agarose Gel Electrophoresis --- p.42 / Chapter 2.3.5 --- Gene Clean Using Sephaglas´ёØ BandPrep Kit (Pharamica) --- p.42 / Chapter 2.3.6 --- Cloning of PCR Products --- p.43 / Chapter 2.3.7 --- Transformation of Competent Cell (Heat Shock Method) --- p.43 / Chapter 2.3.8 --- Small Scale Alkaline Preparation of Plasmid DNA --- p.44 / Chapter 2.3.9 --- Restriction Enzyme Digestion to Release the Insert --- p.45 / Chapter 2.3.10 --- Large Scale Plasmid Preparation of the Positive Clone --- p.45 / Chapter 2.3.11 --- DNA Sequencing of the Positive Clone Using the T7 DNA Polymerase Sequencing Kit (Pharmacia) --- p.46 / Chapter 2.4 --- Results and Discussion --- p.49 / Chapter CHAPTER 3 --- ISOLATION OF GENOMIC CLONES CARRYING THE IGF-I GENE --- p.55 / Chapter 3.1 --- Introduction --- p.55 / Chapter 3.2 --- Materials --- p.56 / Chapter 3.3 --- Methods --- p.58 / Chapter 3.3.1 --- Preparation of the Plating Host Cells --- p.58 / Chapter 3.3.2 --- Phage Titering --- p.58 / Chapter 3.3.3 --- Primary Screening of Common Carp Genomic Library --- p.59 / Chapter 3.3.4 --- Preparation of Radioactive Nucleic Acid Probes --- p.60 / Chapter 3.3.5 --- Purification of the Positive Clones --- p.60 / Chapter 3.3.6 --- Purification of DNA from Lambda Phage Using Sephaglas´ёØ PhagePrep Kit (Pharmacia) --- p.61 / Chapter 3.3.7 --- Restriction Enzyme Digestion Release of Inserts --- p.62 / Chapter 3.3.8 --- Capillary Transfer of DNA to Nylon Membrane Under Alkaline Condition --- p.62 / Chapter 3.3.9 --- Southern Analysis of the 10 Positive Clones --- p.63 / Chapter 3.3.10 --- Restriction Mapping of the Clone P1 --- p.64 / Chapter 3.3.11 --- Subcloning of the Fragments of the Clone PI into Plasmid Vector --- p.64 / Chapter 3.3.12 --- IGF-I Specific PCR --- p.64 / Chapter 3.3.13 --- Amplification of Introns from the Clone P1 Using PCR --- p.67 / Chapter 3.4 --- Results and Discussion --- p.70 / Chapter CHAPTER 4 --- RNA ASSAY USING REVERSE TRANSCRIPTION- POLYMERASE CHAIN REACTION --- p.83 / Chapter 4.1 --- Introduction --- p.83 / Chapter 4.2 --- Materials --- p.85 / Chapter 4.3 --- Methods --- p.86 / Chapter 4.3.1 --- Administration of Hormones --- p.86 / Chapter 4.3.1.1 --- Injection Time Course1 --- p.86 / Chapter 4.3.1.2 --- Injection Time Course2 --- p.86 / Chapter 4.3.2 --- Total RNA Extraction --- p.87 / Chapter 4.3.2.1 --- Rapid RNA Isolation --- p.87 / Chapter 4.3.3 --- Electrophoresis of RNA in Agarose Gel Containing Formaldehyde --- p.88 / Chapter 4.3.4 --- Rapid Isolation of PolyA+ mRNA from Total RNA --- p.89 / Chapter 4.3.5 --- IGF-I Specific RT-PCR --- p.90 / Chapter 4.4 --- Results and Discussion --- p.92 / Chapter CHAPTER 5 --- SEARCH FOR IGF-II GENE USING GENOMIC SOUTHERN BLOT ANALYSIS --- p.101 / Chapter 5.1 --- Introduction --- p.101 / Chapter 5.2 --- Materials --- p.103 / Chapter 5.3 --- Methods --- p.104 / Chapter 5.3.1 --- Preparation of Genomic DNA from Carp Testis --- p.104 / Chapter 5.3.2 --- Restriction Enzyme Digestion of Genomic DNA --- p.104 / Chapter 5.3.3 --- Southern Blotting of the Digested Genomic DNA --- p.104 / Chapter 5.3.4 --- Preparation of the Trout IGF-II Specific Probe --- p.104 / Chapter 5.3.5 --- Genomic Southern Hybridization --- p.105 / Chapter 5.4 --- Results and Discussion --- p.106 / Chapter CHAPTER 6 --- GENERAL DISCUSSION AND CONCLUSION --- p.109 / REFERENCES --- p.112

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 180-226). Available also in a digital version from Dissertation Abstracts.