Structure, developmental expression, and physiological regulation of zebrafish IGF binding protein-1

Endocrinology. 2002 Jul;143(7):2722-31. doi: 10.1210/endo.143.7.8905.


The biological activity and availability of IGFs are regulated by a group of secreted proteins that belong to the IGF-binding protein (IGFBP) gene family. Although six IGFBPs have been identified and studied in mammals, their nonmammalian orthologs remain poorly defined. In this study, we cloned and characterized the full-length zebrafish IGFBP-1. Sequence analysis indicated that its structure is homologous to mammalian IGFBP-1. Using in situ RNA hybridization and RT-PCR, we discovered that IGFBP-1 mRNA was present in all early embryonic stages albeit at very low levels. IGFBP-1 mRNA was initially expressed in multiple embryonic tissues but became restricted to the liver shortly after hatching. In the adult stage, IGFBP-1 mRNA was found only in the liver at low levels. Prolonged food deprivation caused a significant increase in the hepatic IGFBP-1 mRNA levels, and refeeding restored the IGFBP-1 mRNA to the basal levels. When adult fish or embryos were subjected to hypoxic conditions, the IGFBP-1 mRNA expression increased dramatically. Intriguingly, the hypoxia-induced IGFBP-1 expression operated in different embryonic tissues in a developmental-stage-dependent manner. In early embryos, hypoxia-stimulated IGFBP-1 mRNA expression in the pharyngeal arches, ventricle, atrium, and brain. After hatching, the hypoxia-induced IGFBP-1 expression became liver specific. These results not only provide new information about the structural conservation, developmental expression, and physiological regulation of the IGFBP-1 gene but also present the opportunity to elucidate the developmental role of IGFBP-1 using a unique vertebrate model organism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • Databases, Factual
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / physiology*
  • Hypoxia / metabolism
  • In Situ Hybridization
  • Insulin-Like Growth Factor Binding Protein 1 / biosynthesis*
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Insulin-Like Growth Factor Binding Protein 1 / physiology
  • Liver / embryology
  • Liver / metabolism
  • Molecular Sequence Data
  • Nutritional Physiological Phenomena
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution
  • Zebrafish


  • Insulin-Like Growth Factor Binding Protein 1
  • RNA, Messenger