EFFECTS OF THYROPARATHYROIDECTOMY, PARATHYROID-HORMONE, AND PTHRP ON KIDNEYS OF OVINE FETUSES

The fetal parathyroid glands and parathyroid hormone-related protein (PTHrP) have been shown to be important regulators of fetal calcium metabolism through their actions on the placenta and bone. This study examined the effects of fetal thyroparathyroidectomy (with thyroxine replacement) and exogenous infusion of human parathyroid hormone [PTH-(1-34)], PTHrP-(1-34), and PTHrP-(1-141) on the urinary excretion of calcium in chronically cannulated ovine fetuses during the last one-fifth of gestation. Fetal plasma total and ionized calcium concentrations were significantly lower in thyroparathyroidectomized (TxPTx) fetuses when compared with intact fetuses, but there were no significant differences in urinary excretion rates of total calcium. However, TxPTx produced a significant increase in the fractional excretion rate of total calcium and a significant decrease in the excretion of adenosine 3',5'-cyclic monophosphate (cAMP) compared with intact fetuses. Infusions of PTH-(1-34), PTHrP-(1-34), and PTHrP-(1-141) into the jugular vein of TxPTx fetuses (n = 5) at the rate of 1 nmol/h for 2 h, after a 1-nmol loading dose, significantly decreased the excretion rate of total calcium and increased the excretion rate of cAMP in fetal urine. Infusions of all three peptides resulted in significant increases in the concentration of total calcium in fetal plasma but had no effect on the plasma concentrations or urinary excretion rates of phosphate. Infusion of either PTH-(1-34), PTHrP-(1-34), or PTHrP-(1-141) also resulted in an increase in fetal urine osmolality and pH and a decrease in free water clearance in TxPTx fetuses. Infusions of PTHrP-(1-34) at the rate of 1 nmol/h, after a 1-nmol loading dose, into intact fetuses (n = 4) had no effect on the urinary excretion rates or the plasma concentrations of total calcium or phosphate. It was concluded that the fetal parathyroid glands and PTHrP may play an important role in the regulation of fetal renal function.