A Low Molecular Weight Insulin-Like Growth Factor Binding Protein from Rat: cDNA Cloning and Tissue Distribution of its Messenger RNA

Abstract

Rat serum contains two major forms of insulin-like growth factor (IGF) binding proteins (BPs) that have apparent mol wts of about 35,000 and 150,000. We have isolated a cDNA clone encoding an IGF-BP whose N-terminal sequence is completely homologous to the NH2-terminal of the Buffalo rat liver cells-3A BP. The 270 amino acid mature protein has a predicted mol wt of 29,500. It contains a cysteine rich domain at each end of the molecule and an Arg-Gly-Asp (RGD) tripeptide motif near its C-terminus which suggests that this BP might associate with integrin cell surface receptors. The mature protein shares only partial homology with two published human IGF-BPs. Northern blot analysis shows that its mRNA is abundant in several fetal tissues, in adult brain, testes, ovaries, and kidney. Expression in the liver is high in fetal life but decreases to a barely detectable level in adulthood. However, upon hypophysectomy, the mRNA level increases at least 20-fold which suggests a hormonal regulation for the hepatic production of this small IGF-BP.

Changes in IGF-I and -II, IGF Binding Protein, and IGF Receptor Transcript Abundance after Uterine Artery Ligation

“…The importance of placental IGF-I1 expression in the growth retardation of this organ is supported by observations that IGF-I1 is expressed in placenta from early in gestation (40) and that IUGR mice with a disrupted IGF-I1 allele and absent placental IGF-I1 expression have very small placentas (41). IGFBP-2 also may play a role in placental growth, inasmuch as it is expressed in high levels in normal placentas (42) and expression remains high in IUGR when IGF-I1 mRNA abundance declines. The usual pattern of concordance between IGF-I1 and IGFBP-2 expression in the rat during development (1 3) and the high afinity of IGFBP-2 for IGF-I1 suggest that IGFBP-2 helps modulate the local availability of IGF-11.…”

Maternal Hypoxia as a Model for Intrauterine Growth Retardation: Effects on Insulin-Like Growth Factors and Their Binding Proteins

“…The probe for rat IGFBP-2 was a 1295-bp EcoRI restriction fragment of a 1500-bp cDNA isolated from a rat liver cDNA library and contained the entire coding region (23). The probe for human IGFBP-4 was a 440-bp SmaI restriction fragment of the 1.2-kb cDNA isolated from a human osteosarcoma cell gene library (24).…”

Tri-iodothyronine increases insulin-like growth factor binding protein-2 expression in cultured hepatocytes from hypothyroid rats

“…Although message levels are barely detectable in adult liver, relatively high levels persist in adult brain, testes, ovaries and kidney (Margot et al 1989).…”

“…Hepatic IGFBP-2 transcript is increased by hormonal and metabolic manipulation of adult animals such as fasting, hypophysectomy and diabetes (Böni-Schnetzler et al 1989, Margot et al 1989, Orlowski et al 1990, Ooi et al 1990, Tseng et al 1992. Interestingly, the increase after hypophysectomy is not normalized by growth hormone (GH) treatment (Margot et al 1989, Ooi et al 1990, suggesting a possible involvement of other hormones regulated by pituitary secretion. A candidate for this role could be thyroid hormone: it has been demonstrated that thyroid hormone withdrawal increases the expression of IGFBP-2, in both developing and adult rat liver (Näntö-Salonen et al 1991, Rodriguez-Arnao et al 1994.…”