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1Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, District of Columbia 20057; and 2Division of Renal Diseases and Hypertension, Departments of Medicine, Physiology, and Biophysics, University of Colorado Health Sciences Center, Denver, Colorado 80262
Submitted 20 February 2002 ; accepted in final form 29 February 2004
Growth hormone (GH) is an important factor in the developmental adaptation to enhance Pi reabsorption; however, the nephron sites and mechanisms by which GH regulates renal Pi uptake remain unclear and are the focus of the present study. Micropuncture experiments were performed after acute thyroparathyroidectomy in the presence and absence of parathyroid hormone (PTH) in adult (14- to 17-wk old), juvenile (4-wk old), and GH-suppressed juvenile male rats. While the phosphaturic effect of PTH was blunted in the juvenile rat compared with the adult, suppression of GH in the juvenile restored fractional Pi excretion to adult levels. In the presence or absence of PTH, GH suppression in the juvenile rat caused a significant increase in the fractional Pi delivery to the late proximal convoluted (PCT) and early distal tubule, so that delivery was not different from that in adults. These data were confirmed by Pi uptake studies into brush-border membrane (BBM) vesicles. Immunofluorescence studies indicate increased BBM type IIa NaPi cotransporter (NaPi-2) expression in the juvenile compared with adult rat, and GH suppression reduced NaPi-2 expression to levels observed in the adult. GH replacement in the [N-acetyl-Tyr1-D-Arg2]-GRF-(1-29)-NH2-treated juveniles restored high NaPi-2 expression and Pi uptake. Together, these novel results demonstrate that the presence of GH in the juvenile animal is crucial for the early developmental upregulation of BBM NaPi-2 and, most importantly, describe the enhanced Pi reabsorption along the PCT and proximal straight nephron segments in the juvenile rat.
development; sodium-phosphate cotransporters; parathyroid hormone; antagonist to growth hormone-releasing factor; brush-border membrane vesicles
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