SERUM INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN THE HYPOPHOSPHATEMIC MOUSE - DECREASED ACTIVITY AND ABNORMAL MODULATION BY DIETARY PHOSPHATE

The hypophosphatemic mouse, the murine homologue of X-linked hypophosp hatemia, is characterized by rend defects in phosphate reabsorption an d 1,25-dihydroxy vitamin D-3 (1,25(OH)(2))(2)D-3) production and by an osteoblast dysfunction, In view of the potential importance of insuli n-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 s pecific radioimmunoassays and Western ligand blot analysis, we evaluat ed 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 wer e not significantly different from those in normal mice, but IGFBP-3 l evels were significantly lower (70% of normal, p < 0.05) in the mutant strain. The other IGFBP species appear unchanged, Phosphate supplemen tation normalized serum phosphate levels in Hyp mice and elicited a si gnificant decrease in serum IGF-I levels (23%, p < 0.05) and a further reduction in IGFBP-3 (22%, p < 0.02), Phosphate deprivation induced h ypophosphatemia 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 p resent results indicate that the low serum IGFBP-3 activity in Hyp mic e is not related to hypophosphatemia per se. Based on the documented e ffects of parathyroid hormone (PTH) on IGF-I and IGFBP-3, we propose t hat the secondary hyperparathyroidism displayed by Hyp mice and its ex acerbation by phosphate supplementation may contribute to low IGFBP-3 levels in control Hyp mice and to the decreases in serum IGF-I and IGF BP-3 in phosphate-supplemented Hyp mice.