IGF-I and GH stimulate Phex mRNA expression in lungs and bones and 1,25-dihydroxyvitamin D3 production in hypophysectomized rats

Abstract

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 μg) GH or 300 μg 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 D3 (1,25-(OH)2D3) and serum Pi levels, and renal expression of 25-hydroxyvitamin D3-lα-hydroxylase (lα-hydroxylase), of 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) and of the Na-dependent Pi-cotransporter type I and II (NadPi-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)2D3, and renal lα-hydroxylase mRNA rose concomitantly, whereas expression of NEP in lungs was barely affected and renal 24-hydroxylase mRNA decreased. NadPi-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.