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Serum insulin‐like growth factor binding protein‐3 in the hypophosphatemic mouse: Decreased activity and abnormal modulation by dietary phosphate
Author(s) -
Moriwake T.,
Abribat T.,
Brazeau P.,
Ecarot B.
Publication year - 1995
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650101112
Subject(s) - hypophosphatemia , endocrinology , medicine , parathyroid hormone , insulin like growth factor binding protein , alkaline phosphatase , hyperparathyroidism , somatomedin , chemistry , hypophosphatemic rickets , insulin like growth factor , growth factor , receptor , vitamin d and neurology , biology , rickets , calcium , biochemistry , enzyme
The hypophosphatemic mouse, the murine homologue of X‐linked hypophosphatemia, is characterized by renal defects in phosphate reabsorption and 1,25‐dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ) production and by an osteoblast dysfunction. In view of the potential importance of insulin‐like growth factors (IGFs) in the regulation of these processes and the role of IGF‐binding proteins (IGFBPs) as modulators of IGF action, we asked whether Hyp mice have alterations in IGFs or IGFBPs. Using specific radioimmunoassays and Western ligand blot analysis, we evaluated serum levels of IGFs (IGF‐I and IGF‐II) and IGFBPs, respectively, in normal and Hyp mice. We also examined the effect of dietary phosphate on these parameters. Serum levels of IGF‐I and IGF‐II in Hyp mice were not significantly different from those in normal mice, but IGFBP‐3 levels were significantly lower (70% of normal, p < 0.05) in the mutant strain. The other IGFBP species appear unchanged. Phosphate supplementation normalized serum phosphate levels in Hyp mice and elicited a significant decrease in serum IGF‐I levels (23%, p < 0.05) and a further reduction in IGFBP‐3 (22%, p < 0.02). Phosphate deprivation induced hypophosphatemia in normal mice to a degree similar to that in Hyp mice and did not alter serum levels of IGFBP‐3 and IGF‐I and IGF‐II. The present results indicate that the low serum IGFBP‐3 activity in Hyp mice is not related to hypophosphatemia per se. Based on the documented effects of parathyroid hormone (PTH) on IGF‐I and IGFBP‐3, we propose that the secondary hyperparathyroidism displayed by Hyp mice and its exacerbation by phosphate supplementation may contribute to low IGFBP‐3 levels in control Hyp mice and to the decreases in serum IGF‐I and IGFBP‐3 in phosphate‐supplemented Hyp mice.