dc.contributor.author |
Bloomfield, Francis |
en |
dc.contributor.author |
van Zijl, PL |
en |
dc.contributor.author |
Bauer, Michael |
en |
dc.contributor.author |
Phua, Hui |
en |
dc.contributor.author |
Harding, Jane |
en |
dc.date.accessioned |
2011-02-03T02:32:55Z |
en |
dc.date.issued |
2006-08 |
en |
dc.identifier.citation |
AM J PHYSIOL-ENDOC M 291(2):E333-E339 Aug 2006 |
en |
dc.identifier.issn |
0193-1849 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/6333 |
en |
dc.description.abstract |
We have previously reported (Bauer MK, Breier BH, Bloomfield FH, Jensen EC, Gluckman PD, and Harding JE. J Endocrinol 177: 83-92, 2003) that a chronic pulsatile infusion of growth hormone (GH) to intrauterine growth-restricted ( IUGR) ovine fetuses increased fetal circulating IGF-I levels without increasing fetal growth. We hypothesized acortisol-induced upregulation of fetal hepatic GH receptor (GH-R) mRNA levels, secondary increases in IGF-I mRNA levels, and circulating IGF-I levels, but a downregulation of the type I IGF receptor (IGF-IR) as an explanation. We, therefore, measured mRNA levels of genes of the somatotrophic axis by real-time RT-PCR in fetal and placental tissues of fetuses with IUGR (induced by uteroplacental embolization from 110- to 116-days gestation) that received either a pulsatile infusion of GH (total dose 3.5 mg/day) or vehicle from 117-126 days and in control fetuses (n=5 per group). Tissues were collected at 127 days ( term, 145 days). Fetal cortisol concentrations were significantly increased in IUGR fetuses. However, in liver, GH-R, but not IGF-I or IGF-IR, mRNA levels were decreased in both IUGR groups. In contrast, in placenta, GH-R, IGF-I, and IGF-IR expression were increased in IUGR vehicle-infused fetuses. GH infusion further increased placental GH-R and IGF-IR, but abolished the increase in IGF-I mRNA levels. GH infusion reduced IGF-I expression in muscle and increased GH-R but decreased IGF-IR expression in kidney. IUGR increased hepatic IGF-binding protein (IGFBP)-1 and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion. In conclusion, the modest increases in circulating cortisol concentrations in IUGR fetuses did not increase hepatic GH-R mRNA expression and, therefore, do not explain the increased circulating IGF-I levels that we found with GH infusion, which are likely due to reduced clearance rather than increased production. We demonstrate tissue-specific regulation of the somatotrophic axis in IUGR fetuses and a discontinuity between GH-R and IGF-I gene expression in GH-infused fetuses that is not explained by alterations in phosphorylated STAT5b. |
en |
dc.language |
EN |
en |
dc.publisher |
AMER PHYSIOLOGICAL SOC |
en |
dc.relation.ispartofseries |
AM J PHYSIOL-ENDOC M |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
fetal therapy |
en |
dc.subject |
intrauterine growth restriction |
en |
dc.subject |
RECEPTOR MESSENGER-RNA |
en |
dc.subject |
FACTOR-I RECEPTOR |
en |
dc.subject |
METANEPHRIC DEVELOPMENT |
en |
dc.subject |
THYROID-FUNCTION |
en |
dc.subject |
LATE-GESTATION |
en |
dc.subject |
OVINE FETUS |
en |
dc.subject |
IGF-II |
en |
dc.subject |
INSULIN |
en |
dc.subject |
ONTOGENY |
en |
dc.subject |
CORTISOL |
en |
dc.title |
Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1152/ajpendo.00045.2006 |
en |
pubs.issue |
2 |
en |
pubs.begin-page |
E333 |
en |
pubs.volume |
291 |
en |
dc.rights.holder |
Copyright: 2006 the American Physiological Society |
en |
dc.identifier.pmid |
16507606 |
en |
pubs.end-page |
E339 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
65756 |
en |
pubs.org-id |
Liggins Institute |
en |
pubs.org-id |
LiFePATH |
en |
pubs.record-created-at-source-date |
2010-09-01 |
en |
pubs.dimensions-id |
16507606 |
en |