Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep

Erica J Crespi; Teresa L Steckler; Puliyur S Mohankumar; Vasantha Padmanabhan

doi:10.1113/jphysiol.2005.103929

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Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep

Journal article

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Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep

Erica J Crespi, Teresa L Steckler, Puliyur S Mohankumar and Vasantha Padmanabhan

The Journal of physiology, Vol.572(Pt 1), pp.119-130

04/01/2006

DOI: https://doi.org/10.1113/jphysiol.2005.103929

Handle:

https://hdl.handle.net/2376/117529

PMCID: PMC1779643

PMID: 16484301

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https://doi.org/10.1113/jphysiol.2005.103929View

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Abstract

Animals, Newborn

Fetal Growth Retardation - physiopathology

Gene Expression Regulation - drug effects

Pregnancy

Testosterone - administration & dosage

Animals

Maternal-Fetal Exchange

Insulin-Like Growth Factor Binding Proteins - blood

Female

Sheep

Prenatal Exposure Delayed Effects - physiopathology

Insulin-Like Growth Factor I - metabolism

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, approximately 5 months (prepubertal, the catch-up growth period), and approximately 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.

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Title: Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep
Creators: Erica J Crespi - Reproductive Sciences Program, 300 N. Ingalls Bldg, Rm 1109 SW, Ann Arbor, MI 48109-0404, USA. vasantha@umich.edu
Teresa L Steckler
Puliyur S Mohankumar
Vasantha Padmanabhan
Publication Details: The Journal of physiology, Vol.572(Pt 1), pp.119-130
Academic Unit: Biological Sciences, School of
Publisher: England
Grant note: P01 HD044232 / NICHD NIH HHS R01 HD041098 / NICHD NIH HHS HD 41098 / NICHD NIH HHS P01 HD44232 / NICHD NIH HHS
Identifiers: 99900548327001842
Language: English
Resource Type: Journal article