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Abstract
Insulin-like growth factors I and II (IGF-I, IGF-II) and IGF-binding proteins (IGFBPs)
are important modulators of fetal growth. Fetal growth retardation is a major component
of the fetal alcohol syndrome, which is associated with maternal alcoholism. This
study examined the relationship of IGF-system components to growth retardation induced
by ethanol in fetuses of rats fed equicaloric liquid diets (AF, ad libitum-fed controls; PF, pair-fed controls; EF, ethanol-fed) during gestation. The gene
expression of IGF-I and IGF-II in fetal liver and the concentration of IGFs and IGFBPs
in serum and liver were determined. The mean weight of EF fetuses was 13% and 16%
less (p < 0.01) than that of PF and AF offspring, respectively. The serum concentration of
IGF-I was decreased (p < 0.05) by 17% and 22% in EF as compared with PF and AF fetuses. Fetal body weight
showed positive correlations with fetal serum IGF-I and IGF-II (r = 0.566, p < 0.01, and r = 0.412, p < 0.05, respectively). Fetal liver weight correlated with fetal liver IGF-I and IGF-II,
with r values of 0.514 (p < 0.01) and 0.493 (p < 0.01). Hepatic IGF-II mRNA abundance was decreased (p < 0.05) by 27% and 26% in EF as compared with PF and AF offspring. The level of fetal
liver IGF-I mRNA expression was low but was also reduced comparably in EF pups. IGFBP
content in EF fetal serum was increased (p < 0.05 vs AF), and correlated negatively with fetal body weight (r = −0.505, p < 0.01). The diminished IGF-I and IGF-II gene expression and the reduced tissue and
circulating peptide levels, along with a converse change in serum IGFBP abundance,
may have a role in the pathogenesis of fetal alcohol syndrome.
Abbreviations:
AF (control group given free access to food), EDTA (ethylenediamine tetraacetic acid), EF (ethanol-fed group), IGF (insulin-like growth factor), IGFBP (IGF binding protein), PF (pair-fed group)To read this article in full you will need to make a payment
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References
- A revised conservative estimate of the incidence of FAS and its economic impact.Alcohol Clin Exp Res. 1991; 15: 514-524
- Alcohol teratogenicity in the human: a detailed assessment of specificity, critical period, and threshold.Am J Obstet Gynecol. 1987; 156: 33-39
- Ethanol induced teratogenesis: characterization, mechanisms and diagnostic approaches.Life Sci. 1989; 44: 643-659
- Insulin-like growth factors and their binding proteins.Physiol Rev. 1990; 70: 591-614
- Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations.Endocrine Rev. 1989; 10: 68-91
- Nutritional regulation of IGF-I and IGF binding proteins.Ann Rev Nutr. 1991; 11: 393-412
- Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting.Endocrinology. 1991; 128: 518-525
- Specific decrease in liver insulin-like growth factor-I and brain insulin-like growth factor-II gene expression in energy-restricted rats.J Nutr. 1991; 121: 1979-1986
- Tissue and serum concentrations of somatomedin-C/insulin-like growth factor I in fetal rats made growth retarded by uterine artery ligation.Pediatr Res. 1986; 20: 126-130
- Gene expression of insulin-like growth factors, the type I IGF receptor, and IGF-binding proteins in dexamethasone-induced fetal growth retardation.Endocrinology. 1992; 130: 1424-1432
- Effect of ethanol consumption on maternal and fetal carbohydrate metabolism.J Lab Clin Med. 1984; 105: 176-184
- Maternal ethanol ingestion: effect on maternal and neonatal glucose balance.Am J Physiol. 1986; 251: E178-E184
- Ethanol-induced intrauterine growth retardation: Correlation with placental glucose transfer.Alcohol Clin Exp Res. 1986; 10: 167-170
- Maternal alcohol inhibits fetal glucose uptake and growth.J Neuroteratol Toxicol. 1989; 11: 215-219
- Growth patterns of the offspring of alcohol-fed rats.Growth Dev Aging. 1988; 52: 85-89
- Estimation of tissue concentrations of somatomedinin: 3rd ed. Methods Enzymol. 146. 1987: 227-233
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. - Radioimmunological determination of insulin-like growth factors I and II in normal subjects and in patients with growth disorders and extrapancreatic tumor hypoglycemia.J Clin Invest. 1981; 68: 1321-1330
- Synthesis of insulin-like growth factor II in fetal tissues: translation of IGF-II ribonucleic acid and processing of pre-pro-IGF-II.Endocrinology. 1988; 122: 709-716
- Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay.J Clin Invest. 1977; 60: 648-657
- Identification of a family of insulin-like growth factor II secreted by cultured rat epithelial like cell line 18,54-SF: application of a monoclonal antibody.Endocrinology. 1989; 124: 870-877
- Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction.Anal Biochem. 1987; 162: 156-159
- An alternate method for the visualization of RNA in formaldehyde agarose gels.Focus (BRL Publication). 1990; 12: 23-24
- Isolation of a cDNA clone encoding rat insulin-like growth factor-II precursor.Nature. 1984; 312: 277-280
- Isolation of rat testis cDNAs encoding an insulin-like growth factor-I precursor.DNA. 1987; 6: 325-330
- Ausbel FM Brent R Kingston RE Current protocols in molecular biology. Green-Wiley Interscience Publications, New York1987: 4.9.7 (suppl 23)
- Analysis of serum insulin-like growth factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies.Anal Biochem. 1986; 154: 138-143
- Effect of maternal fasting on fetal growth, serum insulin-like growth factors, and tissue IGF messenger ribonucleic acids.Endocrinology. 1990; 126: 2062-2067
- Tissue and development specific regulation of a complex family of rat insulin-like growth factor I messenger ribonucleic acids.Mol Endocrinol. 1988; 2: 1077-1086
- Insulin-like growth factor carrier proteins in neonatal and adult rat serum are immunologically different: demonstration using a new radioimmunassay for the carrier protein from BRL-3A rat liver cells.Endocrinology. 1986; 118: 1743-1758
- Low somatomedin C and high growth hormone levels in newborns damaged by maternal alcohol abuse.Obstet Gynecol. 1989; 74: 366-370
- Cellular pattern of insulin-like growth factor I (IGI) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression.Mol Endocrinol. 1990; 4: 1386-1388
- Insulin-like growth factor-I (IGF-I) and IGF-II hormonal action in cultured rat granulosa cells: mediation via type I but not type II IGF receptors.Endocrinology. 1990; 126: 216-222
- Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor.Mol Endocrinol. 1989; 3: 1701-1709
- Placental blood flow in rats fed alcohol before and during gestation.Life Sci. 1981; 29: 1153-1159
- Diminished insulin-like growth factor-1 levels after chronic ethanol: relationship to pulsatile growth hormone release.Alcohol Clin Exp Res. 1989; 13: 3-7
- The response of rat brain protein synthesis to ethanol and sodium barbital.Alcohol Drug Res. 1987; 7: 243-258
- Circulating levels of insulin, insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins in the small for gestational age fetal rat.Endocrinology. 1993; 132: 327-336
- Production of the rat type 1 insulin-like growth factor-binding protein by well differentiated H4EIIC3 hepatoma cells: identification, purification, and N-terminal amino acid analysis.Endocrinology. 1990; 127: 789-797
- Dose-response characteristics for suppression of low molecular weight plasma insulin-like growth factor-binding protein by insulin.J Clin Endocrinol Metab. 1989; 68: 135-140
- Ethanol ingestion during pregnancy: effects on pregnant rats and their offspring.J Nutr. 1982; 112: 98-103
- Banting lecture 1980. Of pregnancy and progeny.Diabetes. 1980; 29: 1023-1035
.Article info
Publication history
Accepted:
February 3,
1994
Received in revised form:
February 2,
1994
Received:
December 1,
1992
Footnotes
☆Supported in part by the Department of Veterans Affairs and National Institute of Alcohol Abuse and Alcoholism Grants R01 AA06639 and R01 AA08029.
☆☆An editorial relevant to this article appears on p. 149 of this issue of the Journal.
Identification
Copyright
© 1994 Published by Elsevier Inc.
