Presence of insulinlike growth factor receptors and lack of insulin receptors on fetal bovine smooth muscle cells |
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Authors: | Phillip D K Lee Raymond L Hintz Ron G Rosenfeld William E Benitz |
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Institution: | (1) Department of Pediatrics, Stanford University, 94305 Stanford, California;(2) The Children's Hospital, 1056 East 19th Avenue, 80218 Denver, CO |
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Abstract: | Summary Previous investigations have demonstrated specific receptors and associated mitogenic actions for insulin and insulinlike
growth factors I and II (IGF-I and II) in postnatal bovine aortic smooth muscle. Using fetal tissue we have observed different
patterns of binding and action for these peptides.
Smooth muscle cells isolated from near-term fetal bovine aortae were studied in early passage. Specific receptors for both
IGF-I and IGF-II were identified. Specific binding averaged 5.7%/2.5×105 cells for IGF-I, and 16.2% for IGF-II, and 0.3% for insulin. High affinity K
d
for both IGF receptors were nanomolar. IGF-II was fivefold less potent than IGF-I in displacing IGF-I binding. IGF-I showed
no affinity for the IGF-II receptor. Insulin, at physiologic concentrations, was incapable of displacing either IGF-I or IGF-II
binding. Cellular incorporation of methyl-3H]thymidine was stimulated at the lowest dose of IGF-I tested, 0.5 ng/ml. IGF-II showed no effect up to 100 ng/ml, after which
a sharp increase in incorporation was noted. Insulin had a similar effect only at concentrations >0.5 μg/ml, with a maximal
response noted at 5 to 10 μg/ml.
Our results indicate that fetal bovine aortic smooth muscle cells have an abundance of IGF receptors but lack specific insulin
receptors. In addition, IGF-II binding levels are three times higher than for IGF-I. These results are consistent with observations
in other species, in which a predominance of IGF over insulin receptors has been demonstrated in fetal tissue, and provide
further evidence for a role for the IGFs in embryonic cellular metabolism.
This project was supported by grants AM22190 (R. L. H.), AM28229 (R. G. R.) from the National Institutes of Health, Bethesda,
MD, and Research Career Development Award AM01275 from the NIH (R. G. R.). Dr. Lee was the recipient of a fellowship award
from the Juvenile Diabetes Foundation International and is currently supported by funds from the American Diabetes Association.
Dr. Benitz is the recipient of a Clinician-Scientist Award from the American Heart Association, with funds contributed in
part by the California Affiliate. |
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Keywords: | insulinlike growth factors insulin receptors smooth muscle cells growth factor receptors |
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