Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat

T. Unterman, R. Lascon, Michael Gotway, D. Oehler, A. Gounis, R. A. Simmons, E. S. Ogata

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Insulin-like growth factors (IGFs) circulate in association with a family of specific binding protiens (BPs). Recently, we reported that circulating levels of IGFBP-1 and IGFBP-2 are increased in streptozotocin-diabetic adult rats and are differentially regulated in accordance with insulin and metabolic status. Since IGF BPs appear to be important modulators of IGF bioactivity in post-natal life, we asked whether serum levels of IGF BPs also might be altered in utero when the delivery of maternal nutrients is restricted and fetal growth is impaired. Bilateral uterine artery ligation or sham surgery was performed on maternal rats on d 19 of gestation (term 21.5 d). One day after ligation (d 20), fetuses were (SGA) compared to shams (3.1 ± 0.1 vs 3.7 ± 0.2 g, p < .02) and serum levels of glucose (70 ± 5) vs 96 ± 6 mg/dl, p < .01) and insulin (62 ± 4 vs 138 ± 14 μU/mL) also were reduced. In contrast, serum [125I]IGF-I binding activity was markedly increased in SGA litters compared to sham (65 ± 5% maximum binding with 2.5 μL/mL SGA serum vs 14 ± 3% or sham serum, p < .001), and correlated with fetal weight (r = 0.539, p < .05) and insulin (r = 0.622, p < .05). Ligand blotting with [125I]IGF-I revealed that serum levels of IGFBP-1 (32 K) were greater in SGA than shams, while immunoblotting with specific antiserum demonstrated that levels of IGFBP-2 (34 K), the major fetal rat IGF BP, were similar in serum from SGA and shams litters. Affinity labeling and immunoprecipitation confirmed that IGF binding activity is increased in SGA, due largely to increased availability of IGFBP-1. In addition, Northern analysis of hepatic RNA revealed that the abundance of IGBFP-1 mRNA is increased in the SGA fetal rat, while hepatic mRNA for IGFBP-2 is similar in SGA and sham-operated litters. We conclude that circulating levels of IGFBP-1 and the abundance of hepatic mRNA are increased in the SGA fetal rat. IGFBP-1 may be an important modulator of IGF bioactivity and somatic growth in utero.

Original languageEnglish (US)
Pages (from-to)2035-2037
Number of pages3
JournalEndocrinology
Volume127
Issue number4
StatePublished - 1990
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
Gestational Age
Somatomedins
Messenger RNA
Liver
Insulin-Like Growth Factor Binding Protein 2
Serum
Insulin
Insulin-Like Growth Factor I
Ligation
Mothers
Uterine Artery
Fetal Weight
Streptozocin
Fetal Development
Immunoprecipitation
Immunoblotting
Immune Sera
Fetus
RNA

ASJC Scopus subject areas

  • Medicine(all)
  • Endocrinology

Cite this

Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat. / Unterman, T.; Lascon, R.; Gotway, Michael; Oehler, D.; Gounis, A.; Simmons, R. A.; Ogata, E. S.

In: Endocrinology, Vol. 127, No. 4, 1990, p. 2035-2037.

Research output: Contribution to journalArticle

Unterman, T. ; Lascon, R. ; Gotway, Michael ; Oehler, D. ; Gounis, A. ; Simmons, R. A. ; Ogata, E. S. / Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat. In: Endocrinology. 1990 ; Vol. 127, No. 4. pp. 2035-2037.
@article{2f2bb5b9e1f3487cbb29a6a0cda7e347,
title = "Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat",
abstract = "Insulin-like growth factors (IGFs) circulate in association with a family of specific binding protiens (BPs). Recently, we reported that circulating levels of IGFBP-1 and IGFBP-2 are increased in streptozotocin-diabetic adult rats and are differentially regulated in accordance with insulin and metabolic status. Since IGF BPs appear to be important modulators of IGF bioactivity in post-natal life, we asked whether serum levels of IGF BPs also might be altered in utero when the delivery of maternal nutrients is restricted and fetal growth is impaired. Bilateral uterine artery ligation or sham surgery was performed on maternal rats on d 19 of gestation (term 21.5 d). One day after ligation (d 20), fetuses were (SGA) compared to shams (3.1 ± 0.1 vs 3.7 ± 0.2 g, p < .02) and serum levels of glucose (70 ± 5) vs 96 ± 6 mg/dl, p < .01) and insulin (62 ± 4 vs 138 ± 14 μU/mL) also were reduced. In contrast, serum [125I]IGF-I binding activity was markedly increased in SGA litters compared to sham (65 ± 5{\%} maximum binding with 2.5 μL/mL SGA serum vs 14 ± 3{\%} or sham serum, p < .001), and correlated with fetal weight (r = 0.539, p < .05) and insulin (r = 0.622, p < .05). Ligand blotting with [125I]IGF-I revealed that serum levels of IGFBP-1 (32 K) were greater in SGA than shams, while immunoblotting with specific antiserum demonstrated that levels of IGFBP-2 (34 K), the major fetal rat IGF BP, were similar in serum from SGA and shams litters. Affinity labeling and immunoprecipitation confirmed that IGF binding activity is increased in SGA, due largely to increased availability of IGFBP-1. In addition, Northern analysis of hepatic RNA revealed that the abundance of IGBFP-1 mRNA is increased in the SGA fetal rat, while hepatic mRNA for IGFBP-2 is similar in SGA and sham-operated litters. We conclude that circulating levels of IGFBP-1 and the abundance of hepatic mRNA are increased in the SGA fetal rat. IGFBP-1 may be an important modulator of IGF bioactivity and somatic growth in utero.",
author = "T. Unterman and R. Lascon and Michael Gotway and D. Oehler and A. Gounis and Simmons, {R. A.} and Ogata, {E. S.}",
year = "1990",
language = "English (US)",
volume = "127",
pages = "2035--2037",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) and hepatic mRNA are increased in the small for gestational age (SGA) fetal rat

AU - Unterman, T.

AU - Lascon, R.

AU - Gotway, Michael

AU - Oehler, D.

AU - Gounis, A.

AU - Simmons, R. A.

AU - Ogata, E. S.

PY - 1990

Y1 - 1990

N2 - Insulin-like growth factors (IGFs) circulate in association with a family of specific binding protiens (BPs). Recently, we reported that circulating levels of IGFBP-1 and IGFBP-2 are increased in streptozotocin-diabetic adult rats and are differentially regulated in accordance with insulin and metabolic status. Since IGF BPs appear to be important modulators of IGF bioactivity in post-natal life, we asked whether serum levels of IGF BPs also might be altered in utero when the delivery of maternal nutrients is restricted and fetal growth is impaired. Bilateral uterine artery ligation or sham surgery was performed on maternal rats on d 19 of gestation (term 21.5 d). One day after ligation (d 20), fetuses were (SGA) compared to shams (3.1 ± 0.1 vs 3.7 ± 0.2 g, p < .02) and serum levels of glucose (70 ± 5) vs 96 ± 6 mg/dl, p < .01) and insulin (62 ± 4 vs 138 ± 14 μU/mL) also were reduced. In contrast, serum [125I]IGF-I binding activity was markedly increased in SGA litters compared to sham (65 ± 5% maximum binding with 2.5 μL/mL SGA serum vs 14 ± 3% or sham serum, p < .001), and correlated with fetal weight (r = 0.539, p < .05) and insulin (r = 0.622, p < .05). Ligand blotting with [125I]IGF-I revealed that serum levels of IGFBP-1 (32 K) were greater in SGA than shams, while immunoblotting with specific antiserum demonstrated that levels of IGFBP-2 (34 K), the major fetal rat IGF BP, were similar in serum from SGA and shams litters. Affinity labeling and immunoprecipitation confirmed that IGF binding activity is increased in SGA, due largely to increased availability of IGFBP-1. In addition, Northern analysis of hepatic RNA revealed that the abundance of IGBFP-1 mRNA is increased in the SGA fetal rat, while hepatic mRNA for IGFBP-2 is similar in SGA and sham-operated litters. We conclude that circulating levels of IGFBP-1 and the abundance of hepatic mRNA are increased in the SGA fetal rat. IGFBP-1 may be an important modulator of IGF bioactivity and somatic growth in utero.

AB - Insulin-like growth factors (IGFs) circulate in association with a family of specific binding protiens (BPs). Recently, we reported that circulating levels of IGFBP-1 and IGFBP-2 are increased in streptozotocin-diabetic adult rats and are differentially regulated in accordance with insulin and metabolic status. Since IGF BPs appear to be important modulators of IGF bioactivity in post-natal life, we asked whether serum levels of IGF BPs also might be altered in utero when the delivery of maternal nutrients is restricted and fetal growth is impaired. Bilateral uterine artery ligation or sham surgery was performed on maternal rats on d 19 of gestation (term 21.5 d). One day after ligation (d 20), fetuses were (SGA) compared to shams (3.1 ± 0.1 vs 3.7 ± 0.2 g, p < .02) and serum levels of glucose (70 ± 5) vs 96 ± 6 mg/dl, p < .01) and insulin (62 ± 4 vs 138 ± 14 μU/mL) also were reduced. In contrast, serum [125I]IGF-I binding activity was markedly increased in SGA litters compared to sham (65 ± 5% maximum binding with 2.5 μL/mL SGA serum vs 14 ± 3% or sham serum, p < .001), and correlated with fetal weight (r = 0.539, p < .05) and insulin (r = 0.622, p < .05). Ligand blotting with [125I]IGF-I revealed that serum levels of IGFBP-1 (32 K) were greater in SGA than shams, while immunoblotting with specific antiserum demonstrated that levels of IGFBP-2 (34 K), the major fetal rat IGF BP, were similar in serum from SGA and shams litters. Affinity labeling and immunoprecipitation confirmed that IGF binding activity is increased in SGA, due largely to increased availability of IGFBP-1. In addition, Northern analysis of hepatic RNA revealed that the abundance of IGBFP-1 mRNA is increased in the SGA fetal rat, while hepatic mRNA for IGFBP-2 is similar in SGA and sham-operated litters. We conclude that circulating levels of IGFBP-1 and the abundance of hepatic mRNA are increased in the SGA fetal rat. IGFBP-1 may be an important modulator of IGF bioactivity and somatic growth in utero.

UR - http://www.scopus.com/inward/record.url?scp=0025040961&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025040961&partnerID=8YFLogxK

M3 - Article

VL - 127

SP - 2035

EP - 2037

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -