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Journal of Endocrinology (2004) 183, R1-R9    DOI: 10.1677/joe.1.05989
© 2004 Society for Endocrinology
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RAPID COMMUNICATION

Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets

Doron Bresler1,5, Jan Bruder2, Klaus Mohnike3, William D Fraser4 and Peter S N Rowe5

1 United States Air Force (USAF) Lackland, San Antonio, Texas, USA
2 University of Texas Health Science Center at San Antonio, Dept of Medicine, Floyd Curl Drive, San Antonio, Texas 78229, USA
3 Otto-von-Guericke Universität, Magdeburg, Zentrum f. Kinderheilkunde, Germany
4 University of Liverpool, Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, United Kingdom
5 University of Texas Health Science Center at San Antonio, Dept of Periodontics, Floyd Curl Drive, San Antonio, Texas, 78229, USA

(Requests for offprints should be addressed to P S N Rowe; Email: rowep{at}uthscsa.edu)

MEPE (Matrix Extracellular PhosphoglycoprotEin) expression is markedly elevated in X-linked-hypophosphatemic-rickets (HYP) and tumor-induced osteomalacia (TIO). In normal individuals, circulating serum-levels of MEPE are tightly correlated with serum-phosphorus, parathyroid hormone (PTH) and bone mineral density (BMD). Also, MEPE derived, C-terminal ASARM-peptides are candidate minhibins and/or phosphatonins. Our aims were to determine: 1. whether MEPE-ASARM-peptide(s) are abnormally elevated in HYP/hyp serum, and, 2. whether the ASARM-peptide(s) accumulate in hyp mice kidney renal-tubules. Using a specific competitive ELISA we measured a five fold increase (P=0.007) of serum ASARM-peptide(s) in human HYP patients (normal subjects 3.25 µM n=9; S.E.M.=0.51 and HYP-patients 15.74 µM, n=9; S.E.M.=3.32). A 6.23 fold increase (P=0.008) was measured in hyp male mice compared with their normal male siblings (normal-siblings, 3.73 µM, S.E.M.=0.57, n=3; and hyp-mice 23.4 µM, n=3, S.E.M.=4.01). Renal immuno-histological screening also revealed a dramatic increase of ASARM-peptides in regions anatomically consistent with the proximal convoluted tubules. This study demonstrates for the first time that markedly elevated serum levels of protease-resistant ASARM-peptide(s) occur in HYP/hyp and they accumulate in murine hyp kidneys. These peptides are thus likely responsible for the phosphaturia and defective mineralization in HYP/hyp and TIO.




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