The Mechanism of Parathyroid Hormone Action

There are two principal hypotheses to explain the action of parathyroid hormone on bone. The first is that of McLean and Urist (M6), who postulate a feedback mechanism. They suggest that the labile and accessible mineral of the skeleton can only sustain, by a physicochemical action, the hypoparathyroid plasma calcium concentration of about 

The second hypothesis to explain parathyroid action is that a physicochemical steady state exists between bone mineral and the calcium and phosphate ions of the bathing fluids at all levels of parathyroid activity. On this view, the parathyroids determine by their effect on bone the calcium concentration at which bone and tissue fluid come into equilibrium (M3, Nl, N8). Equilibrium studies with bone in vitro have shed some light on the plausibility of this hypothesis. 

Equilibrium studies with both dead and surviving bone have shown that bone mineral possesses a definable solubility. Powdered calf (N17) and human (M3) bone equilibrated for 24 hours in buffer solutions yield a reproducible solubility product in terms of calcium and phosphate concentrations whether the initial concentrations in the buffer are high or low. This product can be expressed in the terms [Ca] [P]  

Surviving human bone chips reproduce at pH 7.4 higher concentrations of calcium and phosphate than dead bone (B4). The mean 24-hour product [Ca] [P] is about 1500, which is only slightly lower than that in normal tissue fluid. In similar experiments with rat bone, prior treatment of the rats with parathyroid extract yielded a higher calcium concentration and parathyroidectomy a lower calcium concentration in the buffer at equilibrium (R1). 

These experiments show that the solubility of bone mineral can be defined in terms of the concentrations of calcium and phosphate that its solubility is governed by the constant value of die ion product [Ca++] [P04 ] that the product [Ca] [P] approximates the calculated tissue fluid product at pH 6.8 and that surviving bone can sustain a higher product than dead bone at pH 7.4. The results are summarized in Table 2 and compared with the values in typical mammalian extracellular fluid. 

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