ANTIGOITROGENIC AND CALORIGENIC ACTIVITIES OF THYROXINE ANALOGUES IN RATS<sup>1</sup>

Stasilli, Neil R.; Kroc, Robert L.; Meltzer, Robert I.

doi:10.1210/endo-64-1-62

Cited by 94 publications

(36 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, they support the hypothesis that the COX complex is the interaction site for diiodothyronines. This contrasts with previous studies ascribing essentially no physiological potency to diiodothyronines [25,26]. However, in these old studies classical parameters, such as anti-goitrogenic activity, growth promotion or stimulation of basal metabolic rate were considered, which are useful to evaluate the general thyroid hormone potency.…”

Section: Discussionmentioning

confidence: 77%

Interaction of diiodothyronines with isolated cytochromec oxidase

et al. 1994

View full text Add to dashboard Cite

Diiodothyronines (3,3'-T2 and 3,5-T2) stimulate the activity of isolated cytochrome c oxidase (COX) from bovine heart mitochondria. Maximal stimulation of activity (about 50%) is obtained with 3,3'-T2 at pH 6.4 and with 3,5-T2 at pH 7.4. In contrast, 3,5,3'-triiodothyronine (TO exhibited no or little stimulation of COX activity. Binding of the hormones to COX leads to conformational changes as shown by modified visible spectra of the oxidized enzyme. It is suggested that 'short-term' effects of thyroid hormones on mitochondrial respiration are at least partly due to the allosteric interaction of diiodothyronines with the COX complex.

show abstract

Section: Discussionmentioning

confidence: 77%

Interaction of diiodothyronines with isolated cytochromec oxidase

et al. 1994

View full text Add to dashboard Cite

show abstract

“…; n=5. potency of T 3 in anti-goitre assays in vivo (Stasilli et al 1959). However, T 2 has rapid and specific effects on oxidative metabolism in rat liver and in mononuclear blood cells (Horst et al 1989, Kvetny 1992, Lanni et al 1992, Goglia et al 1994.…”

Section: Discussionmentioning

confidence: 99%

3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro

Ball¹,

Sokolov²,

Ww³

1997

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Recent data have suggested that the iodothyronine, 3,5-diiodo-l-thyronine (T 2 ), has selective thyromimetic activity. In vivo, T 2 has been shown to suppress TSH levels at doses that do not produce significant peripheral manifestations of thyroid hormone activity. Furthermore, T 2 has been shown to produce smaller increments in peripheral indices of thyroid status than does T 3 , when doses resulting in equivalent suppression of circulating TSH are compared. We have assessed the selective thyromimetic activity of T 2 in vivo and in vitro, and performed in vitro studies to assess the potential molecular basis for these selective properties. T 2 was 100-fold less potent than T 3 in stimulating GH mRNA levels in GH 3 cells. In contrast, the iodothyronines were almost equivalent in their ability to downregulate TR 2 mRNA levels in this cell line. Both 3,3 -diiodo--thyronine and thyronine exhibited no significant thyromimetic effects on either process. In vivo, doses of T 2 and T 3 that were equivalent in their induction of hepatic malic enzyme (ME) mRNA did not produce equivalent suppression of circulating TSH, with T 2 being only 27% as effective as T 3 . T 2 was up to 500-fold less potent than T 3 in displacing [125 I]-T 3 from in vitro translated specific nuclear receptors (TRs) and GH 3 cell nuclear extracts. Electrophoretic mobility shift assays, assessing the ability of T 2 to produce dissociation of TR 1 homodimers from inverted palindrome T 3 response elements, indicated that T 2 was also 1000-fold less potent than T 3 in this respect. These data confirm that T 2 has significant thyromimetic activity, and that this activity is selective both in vivo and in vitro. However, there are no data to support a selective central effect, T 2 being relatively more potent in stimulating hepatic ME mRNA than in suppression of TSH in vivo. The basis for this differential thyromimetic activity is not selective affinity of the different TR isoforms for T 2 , or divergent properties of T 2 in competitive binding and functional assays in vitro.

show abstract

“…It seems possible, however, that the apparent shunting of T4 from conversion to highly potent T3 (39) to the production of calorigenically inactive rT3 (40,41) or other metabolites of T4 such as tetraiodothyroacetic acid (34,42) may reflect a defense reaction of the body intended to safeguard against excessive metabolic stimulation during illness. Obviously, much further study will be needed before this or an alternative possibility can be established.…”

Section: Discussionmentioning

confidence: 99%

“…Urinary excretion of radioactivity was e:camined in two cases given radioactive rT3. The radioactivity excreted in urine was 40 1 Disappearance from serum of TCA-precipitable and ethanol-extractable radioactivity, presumably representing iodothyronines, after injection of radioactive rT3, T3, and T4 intravenously to euthyroid subjects; the data on mean+SE and the percent dose per liter are plotted against time in hours on a semilogarithmic plot. excreted in urine during the first 24 h after injection of radioactive Ta was 32.6 and 32.8%, respectively in two cases.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Chopra¹

1976

J. Clin. Invest.

302

111

View full text Add to dashboard Cite

A B S T R A C T While 3,3',5'-triiodothyronine (reverse TS, rTs) has been detected both in human serum and in thyroglobulin, no quantitative assessment of its metabolic clearance rate (MCR), production rate (PR), or secretion by the thyroid is yet available. This study examines this information in euthyroid subjects and evaluates it in light of similar information about two other iodothyronines in the thyroid: 3,5,3'-triiodothyronine (Ta) and thyroxine (T4). Thus, it was noted that rTs is cleared from human serum at a much faster rate than are Ts and T4; the mean (±-SE) MCR of rT3 was 76.7±5.4 liters/day in 10 subjects, whereas MCR-T3 and MCR-T4 in 8 of them were 26.0±2.2 liters/day and 1.02±0.06 liters/day, respectively. Therefore, even though the mean serum concentration of rT3, 48+2.8 ng/ 100 ml, was much lower than that (128±6.7 ng/100 ml) of T3, the mean PR-rTs (36.5+2.8 ,ug/day) and the mean PR-T3 (33.5±3.7 Ag/day) were similar; in comparison, the mean serum concentration and PR of T4 were 8.6± 0.5 ,ug/100 ml and 87.0±3.9 Mg/day, respectively. These data and those on the relative proportion of rT3, T3, and Ts in 10 thyroid glands were used to assess the significance of the contribution of thyroidal secretion to PRrTs and PR-Ta. It was estimated that whereas thyroidal secretion may account for about 23.8% of serum T3 (or PR-Ta), it may account for only about 2.5% of serum rTa (or PR-rTs). Since peripheral metabolism of T4 is the only known source of rT3 and Ta other than the thyroidal secretion, it could be calculated that as much as 73.0 Ag or 84% of daily PR-T4 may normally be metabolized by monodeiodination either to T3 or to rT3.MCR and PR of various iodothyronines were also examined in five cases with hepatic cirrhosis, where, as documented previously, serum rT3 may be elevated while Received for publication 2 September 1975 and in revised form 20 February 1976. serum Ta is diminished. The mean MCR-rT3 in these cases (41.0 liters/day) was clearly (P < 0.005) less than that (76.7 liters/day) in normal subjects. This was the case at a time when the mean MCR-Ta (26.7 liters/day) and the mean MCR-T4 (1.19 liters/day) did not differ from those (vide supra) in normal subjects. Distinct from changes in MCRs, the mean PR-rT3 (33.0 Ag/day) was similar to, and the mean PR-T3 (10.1 ug/day) and the mean PR-T4 (66.4 Mg/day) were much less than, the corresponding value in normal subjects. Furthermore, while the ratio of PR-rT3 and PR-T4 (rT3/T4) in individual patients was either supranormal or normal, the ratio of PR-Ta and PR-T4 (T3/T&) was clearly subnormal. The various data suggest that: (a) just as in the case of T3, the thyroid gland is a relatively minor source of rT3; peripheral metabolism of T4 is apparently its major source; (b) the bulk of T4 metabolized daily is monodeiodinated to T3 or to rT3; (c) monodeiodination may be an obligatory step in metabolism of T4; (d) monodeiodination of T4 to rTa is maintained normal or is increased in hepatic cirrhosis at a time when monodeiodination of T4 to Ta is decr...

show abstract

ANTIGOITROGENIC AND CALORIGENIC ACTIVITIES OF THYROXINE ANALOGUES IN RATS¹

Cited by 94 publications

References 0 publications

Interaction of diiodothyronines with isolated cytochromec oxidase

Interaction of diiodothyronines with isolated cytochromec oxidase

3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Contact Info

Product

Resources

About

ANTIGOITROGENIC AND CALORIGENIC ACTIVITIES OF THYROXINE ANALOGUES IN RATS1

Cited by 94 publications

References 0 publications

Interaction of diiodothyronines with isolated cytochromec oxidase

Interaction of diiodothyronines with isolated cytochromec oxidase

3,5-Diiodo-L-thyronine (T2) has selective thyromimetic effects in vivo and in vitro

An assessment of daily production and significance of thyroidal secretion of 3, 3', 5'-triiodothyronine (reverse T3) in man.

Contact Info

Product

Resources

About

ANTIGOITROGENIC AND CALORIGENIC ACTIVITIES OF THYROXINE ANALOGUES IN RATS¹