Cited by 536Growth Hormone and Insulin-like Growth FactorsFibroblast Growth Factor ResearchLiver physiology and pathology

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Insulin-like Growth Factor Binding Protein-1: Recent Findings and New Directions

Lee, P. D. K., Giudice, L. C., Conover, C. A., Powell, D. R.·1997·Experimental Biology and Medicine

DOI 10.3181/00379727-216-44182

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Abstract

In 1988, insulin-like growth factor-binding protein-1 (IGFBP-1) became the first characterized member of a group of structurally related soluble proteins which specifically bind and modulate the actions of the IGFs. Since then, a wealth of information has accumulated regarding the physiology of this dynamic serum protein. In this review, we update our 1993 summary (Lee PDK et al. Proc Soc Exp Biol Med 204:4-29) of the status of IGFBP-1 research. The IGFBP-1 protein sequence contains 12 N-terminal and 6 C-terminal cysteine residues which are conserved in other mammalian IGFBP-1 sequences and amongst other IGFBPs; both of the cysteine-rich regions are required for optimal IGF binding. The nonconserved IGFBP-1 midregion may act as both a hinge which defines ligand binding characteristics and as a specific target for protease activity. Integrin-binding and phosphorylation sites within the IGFBP-1 sequence have functional significance in vitro, but their physiologic relevance in vivo have not been defined. The human IGFBP-1 and IGFBP-3 genes are contiguous and located in close proximity to the homeobox A (HOXA) gene cluster on chromosome 7. The other IGFBP genes, located on chromosomes 2, 12, and 17, are also associated with HOX clusters, suggesting evolutionary linkage of the IGFBP and HOX gene families. Similarities between the hlGFBP-1 and phosphoenolpyruvate kinase (PEPCK) promoters, including regions conferring insulin, glucocorticoid, and cyclic adenosine-monophosphate responses, are consistent with our previous hypothesis that IGFBP-1 is involved in regulation of glucose metabolism. The tissue-specific patterns of IGFBP-1 gene expression in liver, kidney, decidua, and ovary may be due to stimulation of IGFBP-1 transcription by hepatic nuclear factor 1 (HNF1) proteins. Clinical and basic studies of IGFBP-1 physiology have been aided by several recently developed assay methods. Numerous investigations have confirmed that insulin, via inhibition of IGFBP-1 transcription, is the primary determinant of IGFBP-1 expression both in vitro and in viva IGF-I and IGF-II also have specific inhibitory effects on IGFBP-1 expression. Glucocorticoids and cAMP stimulate IGFBP-1 transcription, but these effects are observed only in conditions of low or absent insulin effect. Other stimulants of IGFBP-1 expression include thyroid hormones and epidermal growth factor. Phorbol ester stimulation of IGFBP-1 expression can supersede the effects of insulin in vitro; however, the mechanism and in vivo correlates of this effect have not been determined. Cytokines and, perhaps, growth hormones may affect IGFBP-1 expression, perhaps by altering the regulatory actions of insulin; this effect may have important clinical relevance. IGFBP-1 expression is upregulated in liver and (nonhuman) kidney during postinjury regeneration. The IGF-inhibitory actions of IGFBP-1 has been confirmed by numerous in vitro studies and several in vivo animal investigations, including administration of recombinant IGFBP-1 and IGFBP-1 transgenic models. IGFBP-1 has been shown to inhibit somatic linear growth, weight gain, tissue growth, and glucose metabolism. Moreover, IGFBP-1 appears to be a primary determinant of free IGF-I levels in serum. Excess levels of IGFBP-1 may contribute to growth failure in intrauterine growth restriction and in pediatric chronic renal failure, while low IGFBP-1 levels are associated with obesity and with cardiovascular risk factors in insulin resistance syndromes. Serum IGFBP-1 measurements may be useful biochemical marker in these pathologic conditions. IGFBP-1 is expressed in decidualized stromal cells of the uterine endometrium and in ovarian granulosa cells. IGFBP-1, together with IGFs, insulin, ovarian steroids, cytokines, and other factors, is involved in a complex system which regulates menstrual cycles, ovulation, decidualization, blastocyst implantation, and fetal growth. Models for the role of IGFBP-1 in female reproductive physiology are presented, and evidence for pathophysiologic roles in pre-eclampsia, polycystic ovarian syndrome, and uterine malignancy are reviewed. Very recent data indicates that IGFBP-1 undergoes regulated expression in human osteoblasts. Limited information also suggests that IGFBP-1 may be present in peripheral neurons, and that serum IGFBP-1 may increase during exercise and in critical ilIness. In summary, two major roles for IGFBP-1 in normal physiology can be constructed from current data: (i) As an “endocrine” factor, IGFBP-1 regulates the bio-availability of serum IGF-I, thereby modulating IGF-mediated tissue metabolism. The dominant regulation of IGFBP-1 expression by meal-related changes in hepatic insulin concentrations provides a dynamic link to substrate availability. (ii) As an autocrine/paracrine factor, IGFBP-1 appears to play a crucial role in the female reproductive system and, in particular, the sequence of events leading from ovulation to implantation to successful fetal outcom

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Background
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Background
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Background
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Background
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Background
Production of recombinant salmon insulin-like growth factor binding protein-1 subtypes
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Background
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Self-citation
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Background
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Self-citation
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Self-citation
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Background
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Background
Changes in gene expression during chemical‐induced nephrocarcinogenicity in the Eker rat
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“In contrast, IGFBP-1 has also been implicated in IGF independent actions including cell motility, protein synthesis, and apoptosis [54].”
Background
Lithium chloride inhibits the expression and secretion of insulin-like growth factor-binding protein-1
Lewitt, M., Brismar, K., Ohlson, J., et al. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.171r011 · Cited by 13
Integration of physiological, miRNA ‐ mRNA interaction and functional analysis reveals the molecular mechanism underlying hypoxia stress tolerance in crucian carp ( Carassius auratus )
Li, Y., Wu, S., Huang, J., & Zhao, L. (2024) · The FASEB Journal · doi:10.1096/fj.202302629rr · Cited by 12
“65 Collectively, these results suggested that these DE mRNAs may be closely related to the higher ability of crucian carp to resist hypoxia.”
Maternal serum insulin‐like growth factor‐binding protein‐1 (IGFBP‐1) at 11–13 weeks in pre‐eclampsia
Sifakis, S., Akolekar, R., Kappou, D., Mantas, N., & Nicolaides, K. H. (2011) · Prenatal Diagnosis · doi:10.1002/pd.2682 · Cited by 12
“Consequently, the effect of IGF-I and IGFBP-1 on PE is more likely to be related to their metabolic effects rather than their actions on placentation.”
BackgroundInfluential
Is There A Place for Adjuvant Therapy in IVF?
Segev, Y., Carp, H., Auslender, R., & Dirnfeld, M. (2010) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e3181dbc53f · Cited by 12
“Lower serum IGF-1 concentrations following pituitary desensitization (30) may account for some of the suboptimal responses to gonadotrophin stimulation.”
Background
Insulin-like growth factor-binding protein-1 (IGFBP-1) in goldfish, Carassius auratus: molecular cloning, tissue expression, and mRNA expression responses to periprandial changes and cadmium exposure
Chen, W., Zhang, Z., Dong, H., & Yan, F. (2016) · Fish Physiology and Biochemistry · doi:10.1007/s10695-015-0195-x · Cited by 12
“The expression pattern in various tissues suggests that goldfish IGFBP-1 may be synthesized locally and modulate the local action of IGFs.”
BackgroundInfluential
Physiological Regulation of Growth during Social Ascension in a Group-Living Fish
Culbert, B. M., Balshine, S., & Gilmour, K. M. (2019) · Physiological and Biochemical Zoology · doi:10.1086/702338 · Cited by 12
Mid- to late-gestational maternal nutrient restriction followed by realimentation alters development and lipid composition of liver and skeletal muscles in ovine fetuses
Smith, B. I., Liefeld, A., Vasquez-Hidalgo, M. A., et al. (2021) · Journal of Animal Science · doi:10.1093/jas/skab299 · Cited by 12
Hyperinsulinemia and central adiposity: influence of chronic insulin therapy in type 1 diabetes.
Kabadi, U. M., Vora, A., & Kabadi, M. (2000) · Diabetes Care · doi:10.2337/diacare.23.7.1024 · Cited by 12
Direct regulation of IGF-binding protein 1 promoter by interleukin-1β via an insulin- and FoxO-1-independent mechanism
Shi, L., Banerjee, D., Dobierzewska, A., et al. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00289.2015 · Cited by 12
Glucagon Decreases IGF-1 Bioactivity in Humans, Independently of Insulin, by Modulating Its Binding Proteins
Sarem, Z., Bumke‐Vogt, C., Mahmoud, A. M., et al. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00558 · Cited by 11
Administration of Human Insulin-Like Growth Factor-Binding Protein-1 Increases Circulating Levels of Growth Hormone in Mice
Cingel-Ristić, V., van Neck, J. W., Frystyk, J., et al. (2004) · Endocrinology · doi:10.1210/en.2003-1742 · Cited by 11
“induced increase in insulin levels (14).”
Induction of Insulin-Like Growth Factor Binding Protein-1 Expression in Baboon Endometrial Stromal Cells by Cells of Trophoblast Origin
Jasinska, A. J., Han, V. K. M., Fazleabas, A. T., et al. (2004) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2004.03.005 · Cited by 11
Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B
Nagashima, H., Maeda-Nakamura, K., Iwashita, K., et al. (2006) · Archives of Toxicology · doi:10.1007/s00204-006-0162-5 · Cited by 11
“T. Goto Faculty of Agriculture, Shinshu University, Minamiminowa, Nagano 399-4598, Japan related soluble proteins that speciWcally bind and modulate the actions of insulin-like growth factor-I (IGF-I) and -II (Lee et al. 1997).”
Background
Insulin-Like Growth Factor (IGF) Binding Proteins Modulate the Glucocorticoid-Dependent Biological Effects of IGF-II in Cultured Fetal Rat Hepatocytes*
Menuelle, P., Babajko, S., & Plas, C. (1999) · Endocrinology · doi:10.1210/endo.140.5.6750 · Cited by 11
“IGFBP-1 is expressed largely in the liver and endometrium, suggesting that it plays some specific role in each organ (14, 15).”
Background
Molecular basis of carcinogenesis in diabetic patients (Review)
Matyszewski, A., Czarnecka, A. M., Solarek, W., KORZEŃ, P., SAFIR, I. J., Kukwa, W., & Szczylik, C. A. (2015) · International Journal of Oncology · doi:10.3892/ijo.2015.2865 · Cited by 10
Molecular Characterization and Expression Analysis of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Protein-1 Genes in Qinghai-Tibet Plateau Bos grunniens and Lowland Bos taurus
Chen, Y., Fu, M., Lan, D., et al. (2014) · Asian-Australasian Journal of Animal Sciences · doi:10.5713/ajas.14.0413 · Cited by 10
“Furthermore, IGF-1 can induce the expression of hypoxia inducible factor (HIF1) under hypoxic or ischemic condition, triggering the expression of various target genes that regulate the cellular hypoxic response (Lee et al., 1997; Sugawara et al., 2000; Fukuda et al., 2002; Rajpathak et al., 2009).”
Background
Hypoxia alters phosphorylation status of insulin‐like growth factor ( IGF )‐binding protein‐1 and attenuates biological activities of IGF ‐ I in H ep G 2 cell cultures
Tsunawaki, T., Sakai, K., Momomura, M., Wachi, Y., 松澤, 由., & Iwashita, M. (2013) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.12078 · Cited by 10
“During pregnancy, IGFBP-1 is produced predominantly by the maternal liver and deciduas, and the fetal liver.(10,11) The effects of IGFBP-1 depend on its total concentration and its posttranslational modifications, such as phosphorylation, proteolysis and polymerization.”
Background
Molecular identification of grouper Igfbp1 and its mRNA expression in primary hepatocytes under Gh and insulin
Yang, G., Chen, B., Sun, C., et al. (2019) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2019.06.001 · Cited by 10
Production of two recombinant insulin-like growth factor binding protein-1 subtypes specific to salmonids
Hasegawa, R., Miura, T., Kaneko, N., et al. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113606 · Cited by 10
Metal mixtures modeling identifies birth weight-associated gene networks in the placentas of children born extremely preterm
Eaves, L. A., Bulka, C. M., Rager, J. E., Gardner, A. J., Galusha, A. L., Parsons, P. J., O’Shea, T. M., & Fry, R. C. (2022) · Chemosphere · doi:10.1016/j.chemosphere.2022.137469 · Cited by 10
Implication for the regulation of catabolism drawn from the single insulin-like growth factor binding domain protein (SIBD) gene in the mud crab, Scylla paramamosain
Huang, X., Ye, H., Huang, H., Liu, A., & Feng, B. (2015) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2015.04.014 · Cited by 10
Identification and expression analysis of IGFBP-1 gene from Japanese flounder (Paralichthys olivaceus)
Zhai, W., Zhang, J., Shi, Z., et al. (2012) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2012.01.007 · Cited by 10
Stability of disease-associated antibody titers in pregnant women with type 1 diabetes with or without residual beta-cell function.
Novak, E. J., Örtqvist, E., Nord, E., Edwall, L., Hampe, C. S., Bekris, L. M., Persson, B. E., & Lernmark, Å. (2000) · Diabetes Care · doi:10.2337/diacare.23.7.1019 · Cited by 10
Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India
Heald, A. H., Anderson, S. G., Vyas, A., Siddals, K. W., Patel, J. V., Yates, A. P., Bhatnagar, D., Prabhakaran, D., Hughes, E. A., Rudenski, A. S., et al. (2005) · Diabetologia · doi:10.1007/s00125-005-1871-7 · Cited by 10
“In this context, it is likely that the principal determinant of increased postprandial IGF-I bioavailability is IGFBP-1, owing to the rapid fall in IGFBP-1 following food intake [40, 41].”
Background
Effects of natural 24-epibrassinolide on inducing apoptosis and restricting metabolism in hepatocarcinoma cells
Zhou, H., Zhuang, W., Huang, H., Ma, N., Lei, J., Jin, G., Wu, S., Zhou, S., Zhao, X., Lan, L., et al. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154428 · Cited by 9
The Insulin-like Growth Factor Family as a Potential Peripheral Biomarker in Psychiatric Disorders: A Systematic Review
Fernández-Pereira, C., & Agís‐Balboa, R. C. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062561 · Cited by 12
Insights into the mechanism of shortened developmental duration and accelerated weight gain associated with Wolbachia infection in Hylyphantes graminicola
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Desmopressin increases IGF-binding protein-1 in humans.
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The Role of Insulin-like Growth Factor (IGF) Axis in Early Diagnosis of Pancreatic Adenocarcinoma (PDAC)
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Glucagon and GLP-1 stimulate IGFBP-1 secretion in Hep G2 cells without effect on IGFBP-1 mRNA
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Anthropometry, Carbohydrate and Lipid Metabolism in the East Flanders Prospective Twin Survey: Linkage of Candidate Genes Using Two Sib-Pair Based Variance Components Analyses
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Embryo Implantation
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Estrogen agonists/antagonists may down-regulate growth hormone signaling in hepatocytes–An explanation for their impact on IGF-I, IGFBP-1, and lipoprotein(a)
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New metabolic‐endocrine risk markers in endometrial cancer
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Does the Insulin-Like Growth Factor System Interact with Prostaglandins and Proinflammatory Cytokines During Neurodegeneration?
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Authors: Lee, P. D. K., Giudice, L. C., Conover, C. A., & Powell, D. R.
Affiliations: Mayo Clinic (US)
ORCID: Lee, P. D. K.
Giudice, L. C.
Conover, C. A.
Powell, D. R.
Venue: Experimental Biology and Medicine
Publisher: Frontiers Media SA
Published: 1997-12-01
Volume: 216
Issue: 3
Pages: 319-357
ISSN: 0071-3384 (ISSN-L)
1535-3702
1535-3699
DOI: 10.3181/00379727-216-44182
OpenAlex: W2036466897
Cited by: 523
References: 0
Citations by year: 2026: 1 · 2025: 4 · 2024: 8 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 8 · 2019: 11 · 2018: 10 · 2017: 19 · 2016: 16 · 2015: 16 · 2014: 11 · 2013: 17 · 2012: 14
FWCI: 16.84
Type: journal article
Language: en
Open access: closed
Locations: Experimental Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: IGFBP-1, insulin-like growth factor, IGF binding, cysteine-rich region, protease cleavage, integrin binding, phosphorylation sites, IGFBP-3, chromosome 7, glucose metabolism, glucocorticoids, cyclic AMP, tissue-specific gene expression
MeSH terms: Amino Acid Sequence, Animals, Bone and Bones, Cartilage, Connective Tissue, Female, Gene Expression Regulation, Genitalia, Female, Genitalia, Male, Humans, Kidney, Liver, Male, Molecular Sequence Data, Organ Specificity, Substrate Specificity, Insulin-Like Growth Factor Binding Protein 1, Evolution, Molecular

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Insulin-like Growth Factor Binding Protein-1: Recent Findings and New Directions

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