STEADY-STATE ORGAN DISTRIBUTION AND METABOLISM OF THYROXINE AND 3,5,3'-TRIIODOTHYRONINE IN INTESTINES, LIVER, KIDNEYS, BLOOD, AND RESIDUAL CARCASS OF THE RAT IN-VIVO

We have directly measured the relative distribution nd steady state pool sizes of T4 and T3 in blood and extrathyroidal tissues of the whole euthyroid male rat, plus several steady state T3 and T4 metabolism indices in the whole animal, in eight rats infused se for 7 days with labeled I-125-T3 (T3*) or I-125-T4 (T4*) via implanted minipumps. Liver, kidneys, complete intestine, and residual carcass homogenate extracts and sera were chromatographed on both Sephadex and HPLC. Total tissue T3* and T4* in steady state were assessed and corrected for hormone trapped in residual blood in tissues using radioactive albumin as a vascular marker. Labeled Triac* and/or Tetrac* were prominent among steady state metabolites of T* or T4* in intestines, feces, and residual carcass, but not in liver or kidneys. Extrathyroidal steady state T3 and T4 pools in residual carcass were 52.8 +/- 5.74 (SD)% of total T3 and 41.2 +/- 4.57% of total T4. The largest extrathyroidal organ pools containing exchangeable T3 and T4 were intestines, with 33.1 +/- 5.46% of total (extrathyroidal) T3 and 18.1 +/- 2.80% of total T4, whereas liver and kidney pools, previously reported as the largest measured, had only 8.0 +/- 1.45% and 2.30 +/- 0.26% of total T3 and 8.72 +/- 1.56% and 1.01 +/- 0.111% of total T4, respectively. Whole blood contained 3.6 +/- 0.385% of total T3 and 31.2 +/- 1.70% of total T4. Also, 21.3 +/- 8.2% of total body T4 was converted to T3 in the whole rat (residual carcass + intestines + liver + kidneys), the production rate of T4 was PR4 = 37.1 +/- 5.28 ng/h- 100 g BW and the plasma appearance rate of T3 (PR3min) was 10.6 +/- 2.83 ng/h . 100 g BW. T3 production from extrathyroidal T4 was CR3-4 = 6.63 +/- 0.94 ng/h and the minimum T3 secretion rate (SR3min) was 4.02 +/- 0.94 ng/h, each per 100 g BW, indicating that the thyroid secretes more than 38% of whole body T3 in euthyroid steady state. T4 and T3 plasma clearance rates (PCR) were 1.01 +/- 0.29 (T4) and 23.7 +/4. 36 (T3) ml/h - 100 g BW. Whole rat, extrathyroidal endogenous T4 and T3 pools were 595 +/- 140 ng T4 and 102 +/- 22.2 ng T3, each per 100 g BW; and corresponding T4 and T3 whole-body distribution volumes (VD) were 15.5 +/- 0.97 (T4) and 225 +/- 23.8 (V(D)min for T3) ml/100 g BW, further supporting the notion of hidden T3 pools, as this minimum V(D) estimate for T3 is substantially larger than previously published V(D) estimates. The reservoirs of exchangeable T3 or T4 we found in intestines rank second only to those previously found in the rat thyroid gland.