Fetal and neonatal calcium requirements impose heavy demands on maternal bone and mineral homeostasis. The functional response of maternal osteoblasts to this stress is poorly understood. Therefore, plasma osteocalcin (OC) levels were measured by homologous RIA in age-matched nonpregnant, pregnant, and postpartum ewes to evaluate osteoblast function. In pregnant ewes from day 35 of gestation to term, the plasma OC level was suppressed to 8.2 +/- 0.5 micrograms/liter (mean +/- SEM; n = 36) compared with age-matched nonpregnant ewes (18.3 +/- 1.1 micrograms/liter; n = 39; P less than 0.0005). Plasma OC rose to the nonpregnant value by day 20 postpartum and was elevated above this level for the following 40 days (e.g. 44.0 +/- 5.0 micrograms/liter at 48-53 days; P less than 0.0005). The timing of changes in plasma OC levels and weaning did not correlate. The validity of plasma OC measurement as a marker of osteoblast function was assessed by determining the OC plasma production and clearance rates using an [125I]ovine OC infusion method. The OC plasma production rates in matched controls (n = 6), pregnant (n = 9), and 48-53-day postpartum sheep (n = 7) were 1.5 +/- 0.2, 0.5 +/- 0.04 (P less than 0.001 vs. control), and 3.6 +/- 0.6 mg/day (P less than 0.005 vs. pregnant sheep), respectively. In one ewe studied longitudinally, the OC plasma production rate increased by 15 days after parturition and achieved a 10-fold elevation at 49 days postpartum. The OC plasma clearance rate (3.3 +/- 0.3 liters/h) was the same in control, pregnant, and postpartum ewes. It is concluded that 1) changes in plasma OC levels during and after ovine pregnancy reflected changes in OC production, 2) plasma OC measurements are likely to be a useful index of osteoblast function in pregnancy, and 3) osteoblast function appears to be depressed during ovine pregnancy and enhanced markedly in the interval 20-60 days postpartum. The relationship between osteoblast function, as indicated by OC production, and bone formation remains to be clarified.
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.
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