The metabolism of human calcitonin by the liver and kidneys was studied in dogs. Hormone was infused into anaesthetized animals and plasma samples for radioimmunoassay collected from catheters placed in the aorta, hepatic and renal veins. Compared with arterial levels, 30·1 ± 3·3 (S.E.M.)% less hormone was measured in renal vein samples and 8·3 ± 3·0% less in hepatic vein samples. From estimates of blood volume and renal blood flow, it was calculated that the kidneys removed 8% of the circulating hormone/min. Further studies demonstrated that (i) removal of the kidneys prolonged the disappearance of the hormone, (ii) less than 0·3% of infused stable hormone appeared in urine, (iii) radioactivity in kidneys of dogs infused with 131I-labelled calcitonin was concentrated in the cortex, (iv) this uptake of radioactivity was decreased by prior perfusion with stable hormone, and (v) unlabelled hormone disappeared when incubated with homogenates of kidney. From these findings, it is concluded that the kidney plays the major role in the clearance of human calcitonin from the blood and that this clearance is due probably to enzymic degradation.
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