Hormonal regulation of osteocalcin plasma production and clearance in sheep

Abstract

The plasma osteocalcin (OC) concentration correlates with histological parameters of bone formation and has been used as an index of osteoblast activity. Although the rate of OC synthesis is likely to be a major determinant of the plasma OC level, the contribution of other processes, for example, OC plasma clearance, should be evaluated if changes in the plasma OC concentration are to be interpreted meaningfully. We have treated oophorectomized sheep with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and glucocorticoids to alter the plasma OC concentration and used an 125I-OC infusion method to measure changes in the OC plasma clearance (PCR) and to calculate production (PPR) rates. 1,25-(OH)2D3 (8 micrograms/day by iv injection) increased plasma OC levels from 15.8 +/- 2.1 to 52.7 +/- 5.3 ng/ml (n = 10; P less than 0.0005) and the OC PPR from 0.9 +/- 0.08 to 2.6 +/- 0.17 mg/day (n = 5, P less than 0.0005). There was no effect on the OC PCR. Both triamcinolone acetonide (TA) and cortisol, administered by iv infusion, decreased the plasma OC concentration to less than 4 ng/ml and the OC PPR to less than 0.4 mg/day when infused in the doses 0.05-1.0 mg/h (TA) and 2.0 mg/h (cortisol). TA (0.05 mg/h) decreased plasma OC to an undetectable level within 24 h. The effect of cortisol infusion on the plasma OC level and the OC PPR was dose dependent in the range 0.2-2.0 mg/h. TA, infused at the rates of 0.25 and 1.0 mg/h, increased the OC PCR from 3.0 +/- 0.10 to 4.0 liters/h (P less than 0.005; n = 4) and from 2.6 +/- 0.10 to 3.9 +/- 0.10 liters/h (P less than 0.01; n = 3), respectively. It is concluded that the OC PPR and the plasma OC concentration in sheep are responsive to treatment with 1,25-(OH)2D3 and glucocorticoids. Although the changes in plasma OC concentration were attributable largely to effects on OC production, high infusion rates of the glucocorticoid TA led to a highly significant increase in OC plasma clearance. These findings suggest that alterations in OC clearance may contribute to the changes in plasma OC levels seen in some disease states, for example, glucocorticoid excess.