Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney

Edward Chin, Kathleen Michels, Carolyn A. Bondy

Research output: Contribution to journalArticle

Abstract

Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I]IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF- I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF- binding proteins (IGFBPs). Nonspecific binding was less than 20% of the total for both ligands. Insulin (10-5 mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 ± 8% of [125I]IGF- I binding in glomeruli, 60 ± 7% in the tubulo-interstitial cortex, and 32 ± 7% in the medulla. Insulin produced no detectable decrease in [125I]IGF- II binding in any region. IGF-I (10-8 mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 ± 9%, 35 ± 8%, and 39 ± 12% in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and - 5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo- interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitate expression of IGFBPs in tissue sections.

Original languageEnglish (US)
Pages (from-to)156-164
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume78
Issue number1
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

IGF Type 2 Receptor
Insulin-Like Growth Factor Binding Proteins
Somatomedins
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Binding Sites
IGF Type 1 Receptor
Kidney
Insulin
Ligands
In Situ Hybridization
Messenger RNA
Autoradiography
Epithelium
Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3
Gene expression

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney. / Chin, Edward; Michels, Kathleen; Bondy, Carolyn A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 78, No. 1, 01.01.1994, p. 156-164.

Research output: Contribution to journalArticle

@article{9a4e314248b2419dae9d05162069e657,
title = "Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney",
abstract = "Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I]IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF- I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF- binding proteins (IGFBPs). Nonspecific binding was less than 20{\%} of the total for both ligands. Insulin (10-5 mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 ± 8{\%} of [125I]IGF- I binding in glomeruli, 60 ± 7{\%} in the tubulo-interstitial cortex, and 32 ± 7{\%} in the medulla. Insulin produced no detectable decrease in [125I]IGF- II binding in any region. IGF-I (10-8 mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 ± 9{\%}, 35 ± 8{\%}, and 39 ± 12{\%} in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and - 5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo- interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitate expression of IGFBPs in tissue sections.",
author = "Edward Chin and Kathleen Michels and Bondy, {Carolyn A.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1210/jc.78.1.156",
language = "English (US)",
volume = "78",
pages = "156--164",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney

AU - Chin, Edward

AU - Michels, Kathleen

AU - Bondy, Carolyn A.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I]IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF- I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF- binding proteins (IGFBPs). Nonspecific binding was less than 20% of the total for both ligands. Insulin (10-5 mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 ± 8% of [125I]IGF- I binding in glomeruli, 60 ± 7% in the tubulo-interstitial cortex, and 32 ± 7% in the medulla. Insulin produced no detectable decrease in [125I]IGF- II binding in any region. IGF-I (10-8 mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 ± 9%, 35 ± 8%, and 39 ± 12% in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and - 5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo- interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitate expression of IGFBPs in tissue sections.

AB - Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I]IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF- I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF- binding proteins (IGFBPs). Nonspecific binding was less than 20% of the total for both ligands. Insulin (10-5 mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 ± 8% of [125I]IGF- I binding in glomeruli, 60 ± 7% in the tubulo-interstitial cortex, and 32 ± 7% in the medulla. Insulin produced no detectable decrease in [125I]IGF- II binding in any region. IGF-I (10-8 mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 ± 9%, 35 ± 8%, and 39 ± 12% in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and - 5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo- interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitate expression of IGFBPs in tissue sections.

UR - http://www.scopus.com/inward/record.url?scp=0028032091&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028032091&partnerID=8YFLogxK

U2 - 10.1210/jc.78.1.156

DO - 10.1210/jc.78.1.156

M3 - Article

C2 - 7507121

VL - 78

SP - 156

EP - 164

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -