Renal handling of 3,5,3'-triiodothyronine (T 3) in the dog studied by stopflow analysis

Abstract

In order to investigate the renal handling of 3,5,3'-triiodothyronine (T 3), we studied the clearance of T 3 (CT 3) in dogs and the site of tubular secretion and reabsorption of T 3 in dog kidney using the stopflow technique (Malvin et al.). Four female dogs, weighing between 12.2 and 17.8 kg, were used for CT 3 measurement. Fourteen anesthetized dogs, weighing between 7.8 and 17.5 kg, were used for the stopflow study. After the catheter was inserted into the left ureter, 15% mannitol solution and isotonic saline containing both 0.2% PSP and 0.5% creatinine or 0.1% insulin, were infused and then 10-30 μg/kg of T 3 or 100 μg/kg of T 4 was injected as a bolus. When the urine flow reached a stable state of at least 5 ml/min about one-hr after T 3 or T 4 injection, the ureteral catheter was clamped shut for 10 min. After release of the clamp, 20 fractions of urine, 1 ml each, were collected sequentially. The changes in pH and PSP concentrations were used as indices of urine from the distal and proximal tubules, respectively. Urinary T 3 was determined by RIA. CT 3 was obtained by calculating the ratio of the 24-hr urinary T 3 excretion of the serum free T 3 concentration. CT 3, 51.9 ± 12.3 ml/min, was greater than the clearance of creatinine (Ccr), 23.8 ± 4.7 ml/min, suggesting that T 3 is secreted at the tubules in dogs. Almost immediately after the release of the clamped ureter, the concentration of urinary T 3, corrected with excreted urinary creatinine or inulin, was increased, reaching the maximum value at No.2 or 3 fraction. This maximum urinary T 3 value was followed by decreased concentrations of urinary T 3, reaching the minimum around No. 13-15 fraction. The fraction with the highest urinary T 3 concentration was close to the one with the lowest pH, and the fraction with the lowest urinary T 3 concentration was close to the one with the highest PSP concentration. These data suggest that T 3 might be reabsorbed or metabolized at the level of the proximal tubules and secreted into the urine at the level of the distal tubules.