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IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D(3) production in hypophysectomized rats.

Authors: Zoidis, E  Gosteli-Peter, M  Ghirlanda-Keller, C  Meinel, L  Zapf, J  Schmid, C 
Citation: Zoidis E, etal., Eur J Endocrinol 2002 Jan;146(1):97-105.
Pubmed: (View Article at PubMed) PMID:11751074

OBJECTIVE: X-linked hypophosphatemia, a renal phosphate (Pi)-wasting disorder with defective bone mineralization, is caused by mutations in the PHEX gene (a Pi-regulating gene with homology to endopeptidases on the X chromosome). We wondered whether changes in Phex and neprilysin (NEP) (another member of the family of zinc endopeptidases) mRNA expression could be observed in relation to vitamin D and Pi metabolism during GH- and IGF-I-stimulated growth of hypophysectomized rats. DESIGN: Animals were infused s.c. for 2 days with vehicle, 200 mU (67 microg) GH or 300 microg IGF-I/rat per 24 h. We determined serum osteocalcin and osteocalcin mRNA in bone, Phex mRNA in bone and lungs, serum 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and serum Pi levels, and renal expression of 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), of 25-hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) and of the Na-dependent Pi-cotransporter type I and II (Na(d)Pi-I and -II). RESULTS: As compared with vehicle-treated controls, body weight and tibial epiphyseal width significantly increased in GH- and IGF-I-treated animals. Serum osteocalcin and osteocalcin mRNA levels in bone, Phex mRNA in bone and lungs, serum 1,25-(OH)(2)D(3) and renal 1alpha-hydroxylase mRNA rose concomitantly, whereas expression of NEP in lungs was barely affected and renal 24-hydroxylase mRNA decreased. Na(d)Pi-I and -II gene expression in the kidney and serum Pi levels remained unchanged. CONCLUSIONS: Our findings suggest a coordinate regulation of Phex mRNA expression in lungs and bone and vitamin D metabolism during GH- and IGF-I-stimulated growth.


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Additional Information

CRRD Object Information
CRRD ID: 724649
Created: 2003-10-13
Species: All species
Last Modified: 2003-10-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.