Aluminum-induced decrease in osteocalcin levels in the chick.
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Biomedical subjects
Publications and source records attributed to S C Corlett.
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An assay for plasma osteocalcin (BGP) in ruminants is described. Satisfactory cross-reaction was obtained for bovine BGP in several species, namely ovine, cervine, caprine and human. Sample stability at room temperature, after freezing and thawing and after lyophilization and reconstitution is described. Sheep of both sexes have been used throughout and no significant sex effect has been noted. A series of experiments showed a lack of circadian rhythm of plasma BGP concentration in sheep. Plasma BGP values from sheep ranging in age from 0.25 to 7 years fell exponentially from 300 ng/ml at 0.25 years to approximately 50 ng/ml at 1.25 years of age where it remained until the end of the study at 7 years. Long-term administration of adrenocorticotrophic hormone (ACTH) depressed plasma BGP concentrations, although plasma BGP levels were not affected sufficiently by short-term administration of ACTH to increase plasma cortisol concentrations 10-fold during a period of 4 h. It was confirmed that dietary phosphate deficiency depressed plasma BPG concentrations. It is concluded that neither circadian variation nor the short-term stress of handling and bleeding untrained animals need be considered in sampling sheep for measurement of plasma BGP concentration and that the change with age reflected the pattern of development of skeletal maturity in sheep. Values in both growing and mature sheep were at least 6 times higher than in human subjects, which may reflect the 10-fold higher skeletal growth rate in sheep than in humans. This high skeletal activity in sheep may have been selected for in the development of highly productive breeds.
Plasma osteocalcin, or plasma bone GLA protein (BGP), total plasma alkaline phosphatase activity and urinary hydroxyproline excretion of twenty-four pregnant dairy cows (thirteen in their first or second pregnancy, i.e. low parity, and eleven in their third or more pregnancies, i.e. high parity) were measured from 7 weeks before parturition until 1 week after parturition. Seven weeks before parturition the cows' ration was changed to one containing either 0.22% magnesium (low magnesium, LMg) or 0.82% magnesium (high magnesium, HMg) in the dry matter, and the potassium content of both rations was increased to approximately 4.1% in the dry matter to reduce the absorption of magnesium. Plasma BGP levels decreased significantly (P less than 0.01) as parturition approached while total plasma alkaline phosphatase activity and urinary hydroxyproline excretion did not. Magnesium supply and parity had no significant effect on this decrease. The overall plasma concentration of BGP, total plasma alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio in the prepartum period were affected by parity (P less than 0.05) with higher values in the lower parity cows. A significant positive correlation (r = 0.58, P less than 0.01) was found in all cows between plasma BGP level at parturition and the percentage of the bone surface covered with osteoblasts; however, plasma BGP was not correlated either with other histomorphometric variables or with total alkaline phosphatase activity during this time.
Six sheep were fed a diet with normal phosphorus content for 1 month after which plasma inorganic phosphorus (Pi), calcium, osteocalcin (BGP) and alkaline phosphatase concentrations were measured over a 48 h period. The same animals were then fed a low phosphorus diet for a further month prior to a second sampling period. Plasma Pi and BGP concentrations were significantly reduced after the low phosphorus diet; there was a statistically non-significant rise in plasma calcium but no change in alkaline phosphatase concentrations.
The effect of Ca2+ ion concentration on the 25 hydroxylation of tritiated cholecalciferol (3HD3) was investigated using homogenates of ovine liver from vitamin D replete sheep. A significant decrease in the production of 25 hydroxycholecalciferol (25OHD3) was observed when the concentration of Ca2+ in the homogenate was raised above 0.68 mmol/l by the addition of calcium gluconate. Similarly, a final concentration of 37 mumol EGTA/1 (equivalent to a Ca2+ concentration of 26.5 nmol/l) was associated with a 50% reduction of 25OHD3 production. That is, a broad bell-shaped relationship was observed between the production of 25OHD3 and the Ca2+ concentration in the homogenate. These changes in the rate of production of 25OHD3 were reproduced with hepatocytes from vitamin D replete rats, prepared by collagenase perfusion, using the drugs dantrolene sodium (DaNa) to reduce (ED50 = 57 mmol/l) and veratridine to increase (ED50 = 550 mmol/l) the intracellular Ca2+ concentration. Hepatocytes from vitamin D replete rats also showed a reduction in 25 hydroxylation of D3 (ED50 = 6 ng/ml) in response to the addition of 1-25 dihydroxycholecalciferol (1-25 (OH)2D3). The calmodulin antagonists; W7, compound 48/80, trifluoperazine (TFP) and calmidazolium (R24571) were all found to effect a dose response inhibition of the 25 hydroxylation of cholecalciferol by homogenates of ovine liver. R24571 had a similar inhibitory effect (ED50 = 70 mumol/l) upon the 25 hydroxylase enzyme of rat hepatocytes. It is concluded that the 25 hydroxylation of cholecalciferol in liver of vitamin D replete rats and sheep is calcium sensitive and is reduced in the presence of increased concentrations of 1,25(OH)2D3. Calmodulin may also be involved in the regulation of hepatocyte 25-hydroxylase activity by Ca2+.