The role of parathyroid hormone in the maintenance of plasma calcium levels in rats

Investigations were carried out in rats to determine the relative roles of kidney and bone in the regulation of plasma calcium by parathyroid hormone (PTH). The effects of endogenous PTH were studied by parathyroid ablation. Parathyroid glands were removed by thyroparathyroidectomy (TPTX) since parathyroidectomy appears to release calcitonin and thyroidectomy itself does not alter plasma calcium levels. Changes in plasma calcium, urinary calcium and urinary hydroxyproline were determined 3 hr or 24 hr after TPTX in rats of varying ages and in animals fed a calcium-deficient diet for 30 days to enhance PTH secretion and bone turnover. The following observations were made. 1) Plasma calcium but not hydroxyproline decreased 3 hr after TPTX. 2) The degree of hypocalcemia was inversely related to age. 3) By 24 hr, urinary hydroxyproline had decreased and plasma calcium fallen further. 4) Plasma calcium and urinary hydroxyproline decreased immediately in immature rats and rats fed a calcium-deficient diet. 5) TPTX acutely enhanced urinary calcium excretion. 6) The increase in urine calcium accounted for 8, 12, 45 and 67% of the fall in plasma calcium in 45, 134, 221 and 241 g rats, respectively. 7) In animals fed a low-calcium diet only 4% of the fall in plasma calcium was due to increased calciuria. From these findings we conclude that 1) PTH maintains plasma calcium by enhancing calcium transport from bone, resorption of calcified bone matrix and kidney reabsorption of calcium, 2) PTH-dependent bone resorption does not play an appreciable role in the acute control of plasma calcium except when the rate of bone turnover is high, 3) bone-mediated minute-to-minute regulation of plasma calcium by the hormone may be due instead to calcium transport from bone without osteolysis, and 4) PTHdependent contribution of the kidney to the maintenance of plasma calcium probably increases and surpasses that of bone with age.