This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pulford, B. E. Articles by Ishii, D. N. Search for Related Content PubMed PubMed Citation Articles by Pulford, B. E. Articles by Ishii, D. N.

Uptake of Circulating Insulin-Like Growth Factors (IGFs) into Cerebrospinal Fluid Appears to Be Independent of the IGF Receptors as Well as IGF-Binding Proteins¹

Departments of Physiology and Biochemistry and Molecular Biology, Colorado State University, Fort Collins, Colorado 80523

Address all correspondence and requests for reprints to: Dr. Douglas N. Ishii, Physiology Department, Colorado State University, Fort Collins, Colorado 80523. E-mail: dnishii{at}aurogen.com

Peripheral administration of human insulin-like growth factor (hIGF) results in both uptake of hIGF into the cerebrospinal fluid (CSF) and amelioration of brain injury. We tested the hypotheses that IGF uptake into CSF is independent of IGF receptors and IGF-binding proteins (IGFBP). Adult rats were injected sc with various concentrations of hIGF-I or structural analogs, and serum and CSF were withdrawn for assay 90 min later. An enzyme-linked immunoassay was used that detected immunoreactive hIGF-I and its analogs, but not rat IGF-I, IGF-II, or insulin. Plasma hIGF-I levels increased linearly (r = 0.97) with hIGF-I dose between 25–300 µg/rat. By contrast, uptake into CSF reached saturation above 100 µg, suggesting carrier-mediated uptake. hIGF-II reduced the uptake of hIGF-I into CSF (P < 0.02). Des(1–3)hIGF-I is a hIGF-I analog missing the N-terminal tripeptide, resulting in greatly reduced affinity for IGFBP-1, -3, -4, and -5. Nevertheless, des(1–3)hIGF-I was taken up into CSF. [Leu²⁴]hIGF-I and [Leu⁶⁰]hIGF-I have 20- to 85-fold reduced affinity for the type I IGF receptor, yet both were taken up into CSF in amounts similar to hIGF-I. In addition, hIGF-I and des(1–3)hIGF-I were taken up into CSF, although binding to the type II receptor is extremely weak. These data suggest that uptake of circulating IGF-I into CSF is independent of the type I or II IGF receptors as well as IGF sequestration to IGFBP-1, -3, -4, or -5.

This article has been cited by other articles:

				R. L. Chen, N. A. Kassem, M. Sadeghi, and J. E. Preston Insulin-Like Growth Factor-II Uptake Into Choroid Plexus and Brain of Young and Old Sheep J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 141 - 148. [Abstract] [Full Text] [PDF]

				B. S. McEwen Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain Physiol Rev, July 1, 2007; 87(3): 873 - 904. [Abstract] [Full Text] [PDF]

				W. E. Sonntag, C. Bennett, R. Ingram, A. Donahue, J. Ingraham, H. Chen, T. Moore, J. K. Brunso-Bechtold, and D. Riddle Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E604 - E610. [Abstract] [Full Text] [PDF]

				V. C. Russo, P. D. Gluckman, E. L. Feldman, and G. A. Werther The Insulin-Like Growth Factor System and Its Pleiotropic Functions in Brain Endocr. Rev., December 1, 2005; 26(7): 916 - 943. [Abstract] [Full Text] [PDF]

				E. Carro, C. Spuch, J. L. Trejo, D. Antequera, and I. Torres-Aleman Choroid Plexus Megalin Is Involved in Neuroprotection by Serum Insulin-Like Growth Factor I J. Neurosci., November 23, 2005; 25(47): 10884 - 10893. [Abstract] [Full Text] [PDF]

				M. K. Dalsgaard, P. Ott, F. Dela, A. Juul, B. K. Pedersen, J. Warberg, J. Fahrenkrug, and N. H. Secher The CSF and arterial to internal jugular venous hormonal differences during exercise in humans Exp Physiol, May 1, 2004; 89(3): 271 - 277. [Abstract] [Full Text] [PDF]