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Journal of Endocrinology (2005) 186, 145-155    DOI: 10.1677/joe.1.06113
© 2005 Society for Endocrinology

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Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

S Shaikh, F H Bloomfield, M K Bauer, H H Phua, R S Gilmour and J E Harding

Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand

(Requests for offprints should be addressed to F H Bloomfield; Email: f.bloomfield{at}auckland.ac.nz)

We have previously reported that chronic intra-amniotic supplementation of the late gestation growth-restricted (IUGR) ovine fetus with IGF-I (20 µg/day) increased gut growth but reduced liver weight and circulating IGF-I concentrations. Here we report mRNA and protein levels of IGF-I, the type 1 IGF receptor (IGF-1R) and IGF-binding proteins (IGFBP)-1, -2 and -3 in fetal gut, liver, muscle and placenta from fetuses in that earlier study in an attempt to explain these contrasting results. mRNA and protein were extracted from tissues obtained at post mortem at 131 days of gestation (term, 145 days) from three groups of fetuses (control, IUGR+saline and IUGR+IGF-I, n=9 per group). Control fetuses were unembolised and untreated. In the IUGR groups, growth restriction was induced from 113 to 120 days by placental embolisation; from 120 to 130 days fetuses were treated with daily intra-amniotic injections of either saline or 20 µg IGF-I. mRNA was measured by RT-PCR or real-time RT-PCR, and protein by Western blot. In liver, muscle and placenta, IGF-I mRNA and protein levels were reduced by between 8 and 30% in IGF-I-treated fetuses compared with saline-treated fetuses and controls with no change in IGF-1R mRNA or protein levels. In contrast, in the gut, IGF-I mRNA and protein levels were not significantly altered with IGF-I treatment, but IGF-1R levels were increased, especially in the jejunum. Immunolocalisation demonstrated that IGF-1R expression was confined to the luminal aspect of the gut. mRNA levels of all three IGFBPs were reduced in the gut of IGF-I-treated fetuses, but hepatic expression was significantly increased. These data demonstrated tissue-specific regulation of IGF-I, IGF-1R and IGFBPs-1, -2 and -3 in response to intra-amniotic IGF-I supplementation, though the underlying mechanisms remain obscure.




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S. C. Eremia, H. A. de Boo, F. H. Bloomfield, M. H. Oliver, and J. E. Harding
Fetal and Amniotic Insulin-Like Growth Factor-I Supplements Improve Growth Rate in Intrauterine Growth Restriction Fetal Sheep
Endocrinology, June 1, 2007; 148(6): 2963 - 2972.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Endocrinol. Metab.Home page
F. H. Bloomfield, P. L. van Zijl, M. K. Bauer, H. H. Phua, and J. E. Harding
Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues
Am J Physiol Endocrinol Metab, August 1, 2006; 291(2): E333 - E339.
[Abstract] [Full Text] [PDF]




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