DIRECT MEASUREMENT OF WHOLE-BODY THYROID-HORMONE POOL SIZES AND INTERCONVERSION RATES IN FASTED RATS - HORMONE REGULATION IMPLICATIONS

Food deprivation markedly reduces thyroid hormone levels in mammalian plasma, but existing data are incomplete and equivocal regards extrath yroidal hormone production and other indices of overall hormone econom y. We have used a novel experiment design and analysis to directly mea sure the whole-body rate of conversion of T4 into T3 and several other steady-state whole organism parameters, in 4-day fasted and fed contr ol rats. Trace amounts of I-125-labeled T3 (T3) or T4 (T4) were infuse d for 7 days from osmotic minipumps implanted sc. On day 7, rats were anesthetized, bled, and killed and carcasses were frozen in liquid N2, pulverized, homogenized, and extracted. Extracts and plasma samples w ere chromatographed on both Sephadex and HPLC. Tracer infusion rates, whole rat tissue weights, and steady state tissue, blood, and plasma T 3, T4, and total radioactivity concentrations provided all kinetic par ameters of interest from simple steady state computations. T4 secretio n (SR4) and whole body pool sizes were reduced 49-55% in fasted rats. But the most notable results were that the percent of available extrat hyroidal T4 converted to T3 in fasted [41.6 +/- 7.9% (SD)] was 87% gre ater than that in the fed (22.3 +/- 7.69%) rats and this, in turn, gen erated an absolute rate of production of T3 from T4 not significantly different in fasted vs. fed controls (7.17 +/- 2.40 vs. 7.54 +/- 3.10 ng/h.100 g BW). The surprisingly high 42% conversion ratio in fasting is explained in part by larger T3 blood pools (which are not sites of T3 production from T4) relative to tissue T3 pools in fasted rats, not accounted for in earlier whole-body studies. In contrast with this fi nding of an increased T4 to T3 conversion ratio in fasted rats, based on whole body measurements, T3 plasma concentrations (C(p3)), clearanc e rates (PCR3), appearance rates (PAR3 = PCR3C(p3)), and more conventi onal indirect estimates of the T4 to T3 conversion ratio (100 PAR3/SR4 ) were all substantially reduced, consistent with reports in fasting h umans limited to measurements of T3 and T3 turnover in plasma and inte rpreted as indicative of reduced whole body T4 or T3 conversion. Direc tly measured total T3 extrathyroidal distribution volumes, reduced 55% in the fasted group from 241 +/- 19.5 to 109 +/- 8.14 ml/100 g BW, ar e also of interest because fed rat values are 27-61% greater than virt ually all previous estimates of this index of total body T3. This resu lt supports the hidden T3 pool concept, uncovered further here by our inclusion of intestinal contents, which contain a large fraction of ex changeable whole body T3, excluded in earlier whole body studies. It a ppears that the thyroid hormone regulation system responds to food dep rivation by substantially increasing T3 production from available T4 i n tissues overall. Furthermore, this increase is not inferred by plasm a-borne turnover data alone.