HUMAN STANNIOCALCIN INHIBITS RENAL PHOSPHATE EXCRETION IN THE RAT

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (P-i) reabsorption, H uman STC (hSTC) has recently been cloned and sequenced and is highly h omologous to the fish hormone at the amino acid level, The objective o f this study was to examine the possible effects of hSTC on electrolyt e homeostasis and renal function in the rat, Recombinant hSTC was expr essed in bacteria and purified by metal-ion affinity chromatography an d reverse-phase high performance liquid chromatography, Anesthetized a nimals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogra m of body weight, Control animals received solvent alone, The most eff ective dosage was 5 nmol/kg, which caused significant reductions in bo th absolute and fractional phosphate excretion in comparison with cont rol rats, The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood now, blood pressure, or p lasma electrolytes (Na+, K+, Ca2+, P-i, Mg2+). The maximum effect of h STC on phosphate excretion was observed 60-80 minutes postinjection, L esser effects were obtained with higher and lower dosages of hormone, When renal cortical brush-border membrane vesicles were isolated from control and hormone-treated animals 80 minutes postinjection, the rate of Na+/P-i cotransport was found to be 40% higher in vesicles from ho rmone-treated animals (p < 0.01; 5 nmol hSTC/kg). Together, the renal clearance and membrane vesicle data indicate that hSTC participates in the renal regulation of P-i homeostasis in mammals.