Formation of iodoprotein during the peripheral metabolism of 35,3′-triiodo-l-thyronine-125I in the euthyroid man and rat

122

A B S T R A C T Highly specific antisera to triiodothyronine (T3) were prepared by immunization of rabbits with T3-bovine serum albumin conjugates. Antisera with T3 binding capacity of up to 600 ng/ml were obtained. The ability of various thyronine derivatives to inhibit the binding of T3-MI to anti-T3 serum was found to vary considerably. L-Ts, D-T3 and several triiodoanalogues were potent inhibitors of the reaction. Little inhibition of T3-1"I binding was produced by L-thyroxine (T4) or other tetraiodo-analogues, thyronine or iodotyrosines. Chromatography of several T4 preparations indicated that most of their very slight activity could be ascribed to contamination with T3.Successful assay of Ts in serum was accomplished by the addition of diphenylhydantoin to the assay system. Under these circumstances, recovery of Ta added to serum was excellent, and addition of T4 was without significant effect. Serum Ts concentrations in normal subjects averaged 145 ±25 ng/100 ml (SD). Increased concentrations (429 ±146 ng/100 ml) were observed in hyperthyroid patients whereas those with hypothyroidism had serum Ts levels of 99 ±24 ng/100 ml. Elevated Ts concentrations were found also in hypothyroid patients receiving 25 gg or more of T3 daily and in those receiving 300 ,g of T4 daily. Serial measurements of T3 concentrations in subjects after oral T3 administration revealed peak Ta concentrations 2-4 hr after T3 administration. Intramuscular administration of thyrotropin (TSH) resulted in earlier and more pronounced increases in serum T3 than in serum T4 concentrations.Triiodothyronine (T3)1 was recognized to be a biologically active secretory product of the thyroid gland over a decade ago (1). Recent studies have indicated that it is formed extrathyroidally as well (2, 3). Nevertheless, relatively little information concerning the role of Ts secretion in different thyroid disorders has

Section: Discussionmentioning

confidence: 63%

Triiodothyronine Radioimmunoassay

Lieblich¹,

Utiger²

1972

122

“…Over 90% of the radioactivity was in the form of the injected radioactivity and iodide. Since all experiments were conducted within 24 hr after injection of the tracers, the contribution of nonextractable iodine to the total tissue and plasma radioactivity was negligible (6,7).…”

Section: Methodsmentioning

confidence: 99%

“…All subjects received 5 drops of Lugol's solution three times a day during the study. Plasma samples were subjected to TCA precipitation to remove inorganic iodide and extracted four times with ethanol in order to measure nonextractable iodine as previously described (6). The difference between the TCA-precipitable iodine and nonextractable iodine was considered to be iodothyronine.…”

Section: Df3mentioning

confidence: 99%

See 1 more Smart Citation

Differences in primary cellular factors influencing the metabolism and distribution of 3,5,3′-L-triiodothyronine and L-thyroxine

Oppenheimer¹,

Schwartz²,

Shapiro³

et al. 1970

Self Cite

A B S T R A C T Administration of phenobarbital, which acts exclusively on cellular sites, results in an augmentation of the liver/plasma concentration ratio of L-thyroxine (T4) in rats but no change in the liver/plasma concentration ratio of L-triiodothyronine (T3). Whereas phenobarbital stimulates the fecal clearance rate both of T3 and T4, it increases the deiodinative clearance rate of T4 only. These findings suggest basic differences in the cellular metabolism of T3 and T4. Further evidence pointing to cellular differences was obtained from a comparison of the distribution and metabolism of these hormones with appropriate corrections for the effect of differential plasma binding. The percentage of total exchangeable cellular T4 within the liver (28.5) is significantly greater than the corresponding percentage of exchangeable cellular T3 within this organ (12.3). Extrahepatic tissues bind T3 twice as firmly as T4. The cellular metabolic clearance rate (= free hormone clearance rate) of T3 exceeds that of T4 by a factor 1.8 in the rat. The corresponding ratio in man, 2.4, was determined by noncompartmental analysis of turnover studies in four individuals after the simultaneous injection of T4-'I and T3-2"I. The greater cellular metabolic clearance rate of T3 both in rat and man may be related to the higher specific hormonal potency of this iodothyronine.

“…Thereafter, blood samples were obtained twice a day for 3 days and subsequently once daily until 2 wk after the injection. Serum samples were subjected to trichloracetic acid (TCA) precipitation to remove inorganic iodide and were extracted four times with ethanol in order to measure nonextractable iodine (6), according to the method of Oppenheimer, Schwartz, Shapiro, Bernstein, and Surks (7). The difference between the TCA-precipi- …”

Section: -Labeled L-t4 ( [ 125imentioning

confidence: 99%

Estimation of thyroxine and triiodothyronine distribution and of the conversion rate of thyroxine to triiodothyronine in man.

Inada¹,

Kasagi²,

Kurata³

et al. 1975

120

A B S T R A C T Studies on peripheral metabolism of simultaneously administered 125I-labeled L-thyroxine (['I1]T4) and "1'I-labeled L-triiodothyronine ([.1.I]T3) were performed in five normal subjects, in four patients with untreated hypothyroidism, and in 3 hypothyroid patients made euthyroid by the administration of T4. The fractional turnover rate (Xos) of thyroid hormones irreversibly leaving the site of degradation and the volumes of pool 1 (serum, Vi), of pool 2 (interstitial fluid, V2), and of pool 3 (all tissues, V3) were obtained by using a three-compartment analysis. In addition to the turnover studies, the ratios for the in vivo To to T3 conversion were determined by paper chromatographic study in sera obtained 4, 7, and 10 days after the injection. The rate (K12) of the extrathyroidal conversion of T4 to T3 was also estimated by the compartment analysis. The T3 distribution volume (V3) of pool 3, in which T3 is utilized and degraded, was about 60% of total distribution volume (V = V1 + V2+ V3) in normal subjects, whereas only about 25% of the extrathyroidal T4 pool was in the intracellular compartment, indicating that T3 is predominantly an intracellular hormone. The V3/V ratios of T3 were almost constant in a normal ratio of about 60% in hypothyroid patients before and after treatment. On the other hand, the V3/V ratios of T4 were elevated in patients with untreated hypothyroidism, and they returned almost to the normal range after administration of T4. Thus, the V3/V ratio of T4 bore a significant inverse relation to the free T4 concentration in all subjects (r = -0.68, P < 0.05). The findings suggested a redistribution of T4 into the cellular compartment in patients with untreated hypothyroidism. In normal subjects values for K12 averaged 3.00±0.68% per day of the extrathyroidal T4 pool, and the amount of T3 generated by the conversion of T4 (mean-SD, 17±5 Mg/day) was found to contribute approximately 70% of the daily T3 production (mean +SD, 24±5 /Lg/day). The patients with untreated hypothyroidism had elevated Ku2 (mean+SD, 4.16+0.72% per day). Because of diminution of extrathyroidal T4 pool, the amount of T3 converted from T4 was markedly diminished in the untreated patients (mean+SD, 4+3 jug/day), and it agreed closely with T3 production rate (mean±+SD, 3±2 Mg/day). In the patients treated with T4 K,2 returned almost to the normal range (mean±SD, 2.59+0.47% per day), and the amount of T3 arising from deiodination of T4 (mean±+SD, 24±6 Mg/day) corresponded closely to T3 production rate (mean+SD, 21±5 jug/day). Furthermore, a highly significant correlation was evident in the plots of serum T3 concentrations against the amounts of T3 generated by the conversion of T4 in all subjects (r = + 0.85, P < 0.001). The results indicated that the amount of T3 formed by the extrathyroidal conversion of T4 is a major determinant of serum T3 concentration in normal subjects and in patients with hypothyroidism before and after treatment.