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This Article Full Text Full Text (PDF) All Versions of this Article: 572/1/119    most recent jphysiol.2005.103929v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Crespi, E. J. Articles by Padmanabhan, V. Search for Related Content PubMed PubMed Citation Articles by Crespi, E. J. Articles by Padmanabhan, V. Related Collections Integrative

Departments of
¹ Molecular, Cellular & Developmental Biology
² Pediatrics
³ The Reproductive Sciences Program, University of Michigan, Ann Arbor, MI, USA
⁴ Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA

Experimental elevation of maternal testosterone (T) from 30 to 90 days of gestation leads to intrauterine growth retardation (IUGR) and increased prepubertal growth rate in female lambs. This study tested the hypothesis that prenatal T treatment during mid-gestation alters the trajectory of the fetal insulin-like growth factor (IGF)–insulin-like growth factor binding protein (IGFBP) system to promote IUGR and subsequent postnatal catch-up growth in female lambs. Plasma IGF-I and IGFBPs were measured by radioimmunoassay and Western ligand blot, respectively, on 65, 90 and 140 days (d) of gestation, at birth, 5 months (prepubertal, the catch-up growth period), and 9.5 months (postpubertal). Northern blot analysis was used to measure hepatic mRNA content of IGF system components during fetal stages. At fetal 65 d, plasma protein and hepatic mRNA content of IGFBP-1, an inhibitor of IGF bioactivity, was elevated in prenatal T-treated fetuses although body weight did not differ. There was a transient increase in plasma IGF-I and IGFBP-3 concentrations at fetal 90 d in prenatal T-treated fetuses. Hepatic IGF-I mRNA and plasma IGFBP-3 content were reduced by 140 d when body weight was reduced in prenatal T-treated fetuses. Plasma IGFBP-2 content was significantly reduced in prenatal T-treated newborns, but by 4 months these females had significantly higher circulating IGF-I and IGFBP-3 concentrations and faster growth rates than control females. After puberty, plasma IGF-I remained elevated in prenatal T-treated females. These findings provide evidence that prenatal T excess programmes the developmental trajectory of the IGF/IGFBP system in female sheep to reduce IGF bioavailability during IUGR and increase IGF bioavailability during prepubertal catch-up growth.

(Received 19 December 2005; accepted after revision 13 February 2006; first published online 16 February 2006)
Corresponding author V. Padmanabhan: Reproductive Sciences Program, 300 N. Ingalls Bldg, Rm 1109 SW, Ann Arbor, MI 48109-0404, USA. Email: vasantha{at}umich.edu

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