Studies of the level of plasma calcium, the hypocalcemic and bone resorptive responses to exogenous thyrocalcitonin (TCT), and the uptake of radiocalcium and radiostrontium by the skeleton and soft tissues were performed in intact and thyroparathyroidectomized rats following a single dose of 250 μg of l-thyroxine (acute T4) and after 9-21 days of administration of 125 μg of l-thyroxine 3 times a week (chronic T4). In acute T4 treated rats, the hypocalcemic effect of exogenous TCT was augmented, whereas, with chronic T4 treatment, a reduced effect of exogenous TCT was observed. The excretion of 85Sr derived from the prelabeled skeleton was reduced with both acute and chronic] T4 treatment, and exogenous TCT was normally effective in further reducing the excretion of 85Sr. Chronic treatment with T4 caused mild hypocalcemia, and significantly increased skeletal and soft tissue uptakes of 47Ca and 85Sr. These results in young rats are dissimilar to previous studies in humans and dogs in which the predominant effect of T4 is an enhancement of bone resorption, with resultant hypercalcemia, hypercalciuria and demineralization. The data indicate that, in the growing rat, large doses of T4 have a significant anabolic effect on the calcium metabolism of the skeleton and may promote calcium uptake by certain soft tissues as well.
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