TY  - JOUR
AB  - Objective: Human patients with Duchenne muscular dystrophy (DMD) commonly exhibit a short stature, but the pathogenesis of this growth retardation is not completely understood. Due to the suspected involvement of the growth hormone/insulin-like growth factor 1 (GH/IGF1) system, controversial therapeutic approaches have been developed, including both GH- administration, as well as GH-inhibition. In the present study, we examined relevant histomorphological and ultrastructural features of adenohypophyseal GH-producing somatotroph cells in a porcine DMD model.Methods: The numbers and volumes of immunohistochemically labelled somatotroph cells were determined in consecutive semi-thin sections of plastic resin embedded adenohypophyseal tissue samples using unbiased state-of-the-art quantitative stereological analysis methods.Results: DMD pigs displayed a significant growth retardation, accounting for a 55% reduction of body weight, accompanied by a significant 50% reduction of the number of somatotroph cells, as compared to controls. However, the mean volumes of somatotroph cells and the volume of GH-granules per cell were not altered. Western blot analyses of the adenohypophyseal protein samples showed no differences in the relative adenohypophyseal GH-abundance between DMD pigs and controls.Conclusion: The findings of this study do not provide evidence for involvement of somatotroph cells in the pathogenesis of growth retardation of DMD pigs. These results are in contrast with previous findings in other dystrophin-deficient animal models, such as the golden retriever model of Duchenne muscular dystrophy, where increased mean somatotroph cell volumes and elevated volumes of intracellular GH-granules were reported and associated with DMD-related growth retardation. Possible reasons for the differences of somatotroph morphology observed in different DMD models are discussed.
AU  - Hofmann, I.*
AU  - Kemter, E.*
AU  - Theobalt, N.*
AU  - Fiedler, S.*
AU  - Bidlingmaier, M.*
AU  - Hinrichs, A.*
AU  - Aichler, M.
AU  - Burkhardt, K.*
AU  - Klymiuk, N.*
AU  - Wolf, E.*
AU  - Wanke, R.*
AU  - Blutke, A.
C1  - 57795
C2  - 47960
CY  - Journal Production Dept, Robert Stevenson House, 1-3 Baxters Place, Leith Walk, Edinburgh Eh1 3af, Midlothian, Scotland
SP  - 6-16
TI  - Linkage between growth retardation and pituitary cell morphology in a dystrophin-deficient pig model of Duchenne muscular dystrophy.
JO  - Growth Horm. IGF Res.
VL  - 51
PB  - Churchill Livingstone
PY  - 2020
SN  - 1096-6374
ER  - 

TY  - JOUR
AB  - OBJECTIVE: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied. DESIGN: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6g/100mL) or higher (HP: 2.05 and 3.2g/100mL) protein contents for the first 12months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6months were regressed on determined SNPs and feeding groups in 501 infants. RESULTS: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3ng/mL and ~1.3 and decreased in BF infants by ~0.6ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing. CONCLUSIONS: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.
AU  - Rzehak, P.*
AU  - Grote, V.*
AU  - Lattka, E.
AU  - Weber, M.*
AU  - Gruszfeld, D.*
AU  - Socha, P.*
AU  - Closa-Monasterolo, R.*
AU  - Escribano, J.*
AU  - Giovannini, M.*
AU  - Verduci, E.*
AU  - Goyens, P.*
AU  - Martin, F.*
AU  - Langhendries, J.P.*
AU  - Demmelmair, H.*
AU  - Klopp, N.
AU  - Illig, T.
AU  - Koletzko, B.*
AU  - European Childhood Obesity Trial Study Group (*)
C1  - 26226
C2  - 32132
SP  - 149-158
TI  - Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.
JO  - Growth Horm. IGF Res.
VL  - 23
IS  - 5
PB  - Churchill Livingstone
PY  - 2013
SN  - 1096-6374
ER  - 

TY  - JOUR
AB  - The expression of the insulin-like growth factor II (IGF-II) gene (lgf2) in rodents is completely abrogated in almost all adult tissues. A prominent exception are neoplasms in which IGF-II frequently serves as an autocrine growth factor. We have investigated the potential role of lgf2 expression during liver carcinogenesis. After application of diethylnitrosamine (DEN) preneoplastic foci and adenomas emerged in liver tissue of wildtype and phosphoenolpyruvate carboxykinase (PEPCK)-IGF-II transgenic mice. Surprisingly, number and size of preneoplastic foci were not significantly increased in PEPCK-IGF-II mice as compared with wild-type animals. In situ preparation showed that early adenomas expressed lgf2 transcripts. Reverse transcriptase polymerase chain reaction (RT-PCR) and restriction enzyme analysis confirmed that DEN treatment had indeed reactivated the hepatic expression of murine lgf2 in control mice in a dose-dependent manner. This re-expression of lgf2 persisted for at least 18 months. Species-specific RT-PCR analyses also revealed the presence of murine lgf2 mRNAs in some PEPCK-IGF-II mice. A similar reactivation of lgf2 was detected in bovine growth hormone transgenic mice which develop hepatocellular neoplasms with high frequency. Our results suggest that reactivation of lgf2 is an early event during hepatocarcinogenesis in mice. Its appearance in two independent animal models suggests that lgf2 may be important at pivotal checkpoints of hepatocarcinogenesis.
AU  - Lahm, H.*
AU  - Gittner, K.
AU  - Krebs, O.*
AU  - Sprague, L.*
AU  - Deml, E.
AU  - Oesterle, D.
AU  - Hoeflich, A.*
AU  - Wanke, R.*
AU  - Wolf, E.*
C1  - 10143
C2  - 20305
SP  - 69-79
TI  - Diethylnitrosamine induces long-lasting re-expression of insulin-like growth factor II during early stages of liver carcinogenesis in mice.
JO  - Growth Horm. IGF Res.
VL  - 12
PB  - Churchill Livingstone
PY  - 2002
SN  - 1096-6374
ER  -