Thyroxine-induced stimulation of hepatic cell transport of calcium and magnesium.

The effect of L-thyroxine on the bidirectional transport of calcium and magnesium in rat liver was assessed in vitro. An increase of 34% in the fractional coefficient for calcium influx was observed 24 hr after the administration of 500 mug of thyroxine. Chronic treatment with thyroxine for 1 and 3 wk at a dose of 750 mug/wk resulted in increases in calcium influx of 57 and 51%, respectively. Calcium efflux was increased irregularly, by 14-26%. Magnesium transport measured in a similar system was not altered by 24 or 48 hr of treatment with thyroxine, but continuation of treatment for 1-3 wk resulted in increases in magnesium influx of 47-49%. Magnesium efflux was not significantly affected. Neither increased cellular binding of divalent cations nor enhanced protein synthesis could be incriminated in the stimulatory effect of thyroxine on divalent cation transport. Actinomycin-D and D,L-ethionine, inhibitors of protein synthesis, stimulated calcium and magnesium transport in liver independently of the effects of thyroxine. These data present the possibility that certain actions of thyroid hormone may be mediated or modulated by associated, direct changes in the cellular transport and intracellular concentrations of divalent cations.

The cellular transport of calcium in rat liver.

The bidirectional transport of calcium in rat liver was studied using slices labeled with Ca(47) in a closed two compartment system. Steady-state conditions were observed with influx and efflux transfer coefficients of 0.070 and 0.018 per minute, respectively. The rapidly exchanging cell fraction of calcium existed at a concentration three times higher than the average cell concentration of calcium and occupied cell loci comprising less than 25% of the cell mass, suggesting that calcium associated with the cell membranes, nuclei, and mitochondria participated in the rapidly exchanging fraction. At pH 7.4 and 377deg;C, the influx transfer coefficient was 25% above the steady-state condition and accumulation of calcium by the slices occurred. Studies of the effects of varied physical and chemical conditions revealed that the influx transfer coefficient was increased by elevated pH, strontium, certain metabolic inhibitors, and 2 mM concentrations of cyclic adenosinemonophosphate and adenosinetriphosphate. The influx transfer coefficient was decreased by reduced temperature, decreased pH, magnesium, and 10 mM adenosinetriphosphate. The efflux transfer coefficient was increased by elevated pH, strontium, iodoacetate, and adenosinetriphosphate, and was decreased by reduced temperature and by N-ethylmaleimide. These data support the thesis that cell transport of calcium is accomplished by the attachment of calcium atoms to the cell surface and transport through the plasma membrane bound to either specific carriers or to membrane constituents. Conditions which change the affinities, capacities, and mobilities of plasma membrane ligands that bind calcium or cause extracellular chelation of calcium are capable of altering the rate of calcium transport.

Skeletal turnover and total body elemental composition during extended calcitonin treatment of Paget's disease.

Twenty patients with generalized symptomatic Paget's disease had serial measurements of radiocalcium turnover and/or total body elemental composition by in vivo neutron activation analysis during long-term calcitonin therapy. Despite maintained clinical improvement, seven of 15 patients showed partial or total loss of the initial decelerating effect of calcitonin on skeletal turnover, whereas the remaining eight patients maintained the calcitonin-induced deceleration. The changes in skeletal turnover were roughly proportional to the induced changes in serum alkaline phosphatase and urinary hydroxyproline. However, disparities in the magnitude of the changes among the three parameters were not uncommon. Total body calcium was increased by a mean of 22% above predicted prior to calcitonin and decreased significantly by 4% during long-term calcitonin treatment. Total body phosphorus, nitrogen, and sodium also decreased. The phosphorus and sodium losses appeared to be mostly from the skeleton. These data confirm histologic evidence of the disappearance of pagetic bone, resumption of normal lamelar bone formation, and radiographic evidence of a decrease in bone volume during calcitonin treatment and incidate the relative magnitude of this effect. The action of calcitonin in this regard possibly represents a specific effect on Paget's disease beyond its general skeletal effect of reduce cellular activity.