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Although the metabolic role of the T2 isomers is poorly understood and the absolute contribution of these hormones to physiological function in humans is unclear, experimental data raises doubts whether the various effects of thyroid hormones in different tissues can all be attributed to T3. The isomer 3,5-T2 has selective thyromimetic activity and has an ability to suppress TSH levels.7 In animals, the 3,3'-T2 and 3,5-T2 isomers induce a dose-dependent increase in resting metabolic rate (RMR), an increase accompanied by a parallel increase in the oxidative capacity of metabolically active tissues such as liver, skeletal muscle, brown adipose tissue, and heart. In these experiments, 3,5-T2 exerted its greatest stimulatory effect on brown adipose tissue (BAT), while 3,3'-T2 had its greatest effect on muscle oxidative capacity. Although T3 is generally considered to be the metabolically active thyroid hormone, in contrast to these T2 isomers, T3 has only a small metabolic and oxidative effect on skeletal muscle and no significant stimulatory effect in heart and BAT, irrespective of dose...
1: Metabolism. 1978 Jun;27(6):677-83.Click here to read Links
Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation.
* Burman KD,
* Dimond RC,
* Djuh YY,
* Bruton J,
* Washburn TB,
* Wright FD,
* Wartofsky L.
In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.
PMID: 418309 [PubMed - indexed for MEDLINE]
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Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs.
* Verhoeven FA,
* Van der Putten HH,
* Hennemann G,
* Lamers JM,
* Visser TJ,
* Everts ME.
Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
Cellular and nuclear uptake of [125I]tri-iodothyronine (T3) and [125I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T(3) uptake was measured. Cells (5-10 x 10(5) per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 degrees C in the same medium, 0.5% BSA and [125I]T3 (100 pM), or [125I]Triac (240 pM). Expressed as % dose, T(3) uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0.001) greater than T3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [125I]T3 was competitively inhibited by 10 microM unlabeled T3 (45-52%; P<0.001) or 3,3'- diiodothyronine (T2) (52%; P<0.001), and to a smaller extent by thyroxine (T(4)) (27%; 0.05We conclude that i) Triac is taken up by cardiomyocytes; ii) 3,3'-T2 and, to a lesser extent, DITPA and T4 interfere with plasma membrane transport of T3, whereas 3,5-T2, Triac, or Tetrac do not; iii) the transport mechanism for Triac is probably different from that for T3.
PMID: 12010632 [PubMed - indexed for MEDLINE]
3,3'-Diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors and of healthy subjects during acute stress.
* Pinna G,
* Hiedra L,
* Meinhold H,
* Eravci M,
* Prengel H,
* Brodel O,
* Graf KJ,
* Stoltenburg-Didinger G,
* Bauer M,
* Baumgartner A.
Department of Radiology, Universitatsklinikum Benjamin Franklin, Free University of Berlin, Germany.
In this article we describe the development of a highly sensitive, accurate, and reproducible RIA for the measurement of 3,3'-diiodothyronine (3,3'-T2) in human serum and brain tissue. The detection limits were 1.8 fmol/g and 1.5 pmol/L in human brain tissue and serum, respectively. Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23). The mean serum concentration of 3,3'-T2 in 62 healthy controls was 46.6 +/- 20.0 pmol/L. 3,3'-T2 levels declined significantly with increasing age. They were significantly lower in patients with brain injury (34.2 +/- 19.4 pmol/L; P = 0.006), were at the upper limit of normal in patients with sepsis (57.0 +/- 36.9 pmol/L; P = 0.06), and were elevated in patients with liver disease (72.6 +/- 56.7 pmol/L; P = 0.04) and brain tumors (89.0 +/- 40.9 pmol/L; P = 0.01). The serum levels of T3 were significantly lower than those in controls in all 4 patient groups. Serum concentrations of 3,3'-T2 were significantly enhanced in 9 patients with hyperthyroidism (85.4 +/- 43.0 pmol/L; P = 0.01) and were reduced in 12 patients with hypothyroidism (14.9 +/- 9.2 pmol/L; P = 0.001). In both normal brain tissue, obtained either intraoperatively or excised postmortem, and brain tumors, the concentrations of 3,3'-T2 ranged between 50-300 fmol/g. In healthy controls, 2 different forms of acute stress (sleep deprivation and delivering a lecture) significantly increased serum levels of T4 and T3, but did not affect those of 3,3'-T2 or 3,5-T2. In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2. The production of 3,3'-T2 in NTI seems to be regulated in a disease-specific manner, resulting in unchanged, reduced, or elevated hormone concentrations.
PMID: 9745405 [PubMed - indexed for MEDLINE]
Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats.
* Moreno M,
* Lombardi A,
* Lombardi P,
* Goglia F,
* Lanni A.
Dipartimento di Chimica, Facolta di Scienze, Universita degli Studi di Salerno, Italy.
We have investigated the biological effects of physiological doses of 3,5-diiodo-L-thyronine (3,5-T2) and 3,3'-diiodo-L-thyronine (3,3'-T2) (at doses from 2.5 to 10 microg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by propylthiouracil and iopanoic acid administration. In such animals deiodinase activities were inhibited and thyroid hormones serum levels strongly reduced. The effects of T2s were compared with those elicited by 3,5,3'-triiodo-L-thyronine (T3) (2.5 microg/100 g BW).The serum TSH level was much greater in hypothyroid rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to control (i.e, the level in hypothyroid rats); it thus reached a value not significantly different from that seen in the euthyroid rats. 3,5-T2 produced a similar effect, suppressing the TSH level by about 75% compared to control; it thus reached values not significantly different from those of the euthyroid and T3-treated rats. By contrast, 3,3'-T2 had no effect on TSH, whatever the dose. The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3 administration increased the GH level by about 5-fold, restoring it to the value seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used (from 2.5 to 10 microg/100 g BW), showed increased serum GH levels: at a dose of 10 microg/100 g BW the level reached a value about 5-fold higher than that in hypothyroid rats. This value was not significantly different from those of euthyroid and T3-treated rats. 3,3'-T2 did not affect GH levels whatever the dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum TSH and GH levels in rats.
PMID: 9651103 [PubMed - indexed for MEDLINE]
Interaction of diiodothyronines with isolated cytochrome c oxidase.
* Goglia F,
* Lanni A,
* Barth J,
* Kadenbach B.
Dipartimento di Fisiologia Generale ed Ambientale, Universita degli Studi di Napoli Federico II, Italy.
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 (T3) 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.
PMID: 8013649 [PubMed - indexed for MEDLINE]
Effect of 3,3'-di-iodothyronine and 3,5-di-iodothyronine on rat liver mitochondria.
* Lanni A,
* Moreno M,
* Cioffi M,
* Goglia F.
Dipartimento di Fisiologia Generale ed Ambientale, Universita di Napoli, Italy.
In the present study we report that 3,3',5-tri-iodothyronine (T3) as well as two iodothyronines (3,5-di-iodothyronine (3,5-T2) and 3,3'-di-iodothyronine (3,3'-T2)) significantly influence rat liver mitochondrial activity. Liver oxidative capacity (measured as cytochrome oxidase activity/g wet tissue) in hypothyroid compared with normal rats was significantly reduced (21%, P > 0.01) and the administration of T3 and both iodothyronines restored normal values. At the mitochondrial level, treatment with T3 stimulated respiratory activity (state 4 and state 3) and did not influence cytochrome oxidase activity. On the other hand, both the mitochondrial respiratory rate and specific cytochrome oxidase activity significantly increased in hypothyroid animals after treatment with 3,3'-T2 or 3,5-T2 (about 50 and 40% respectively). The actions of both iodothyronines were rapid and evident by 1 h after the injection. The hepatic mitochondrial protein content which decreased in hypothyroid rats (9.6 mg/g liver compared with 14.1 in normal controls, P < 0.05) was restored by T3 injection, while neither T2 was able to restore it. Our results suggest that T3 and both iodothyronines have different mechanisms of action. T3 acts on both mitochondrial mass and activity; the action on mitochondrial activity was not exerted at the cytochrome oxidase complex level. The action of the iodothyronines, on the other hand, is exerted directly on the cytochrome oxidase complex without any noticeable action on the mitochondrial mass.
PMID: 8381457 [PubMed - indexed for MEDLINE]
Effect of 3,3'-diiodothyronine and 3,5-diiodothyronine on rat liver oxidative capacity.
* Lanni A,
* Moreno M,
* Cioffi M,
* Goglia F.
Department of General and Environmental Physiology, University of Naples, Italy.
We report that 3,5,3'-triiodothyronine (T3) as well as two other iodothyronines (3,3'-diiodothyronine and 3,5-diiodothyronine (T2s)) stimulate rat liver oxidative capacity (measured as cytochrome oxidase activity (COX)). In hypothyroid rats COX activity and mitochondrial protein content are significantly lower than in normal control animals. The administration of both T3 and T2s to hypothyroid rats significantly enhances hepatic COX activity with T3 having the greatest effect (+60%); moreover, T3 restores the mitochondrial protein content whereas the T2s are ineffective. Administration of T2s results in a faster stimulation (already significant 1 h after the injection) of hepatic COX activity than T3 injection. Our results suggest that T3 acts on the protein synthesis mechanism involved in the regulation of the mitochondrial mass while T2s would act directly at the mitochondrial level.
PMID: 1324858 [PubMed - indexed for MEDLINE]
Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states.
* Nishikawa M,
* Inada M,
* Naito K,
* Ishii H,
* Tanaka K,
* Mashio Y,
* Imura H.
To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 6641638 [PubMed - indexed for MEDLINE]
Immediate opposite effect of salicylate on thyroxine and 3,5,3'-triiodothyronine versus 3,3',5'-triiodothyronine level in plasma in rats.
* Langer P,
* Foldes O,
* Brozmanova H,
* Straussova K,
* Gschwendtova K.
In a total of 46 male rats polyethylene tubings were introduced into femoral artery and vein under pentobarbiturate anesthesia. Then heparin (300 U kg-1) was injected at 60-90 min after pentobarbiturate and two control blood samples were subsequently taken. After that sodium salicylate (200 mg kg-1) was injected i.v. and blood samples were taken at 30-420 min later. An immediate decrease of the thyroxine (T4) level in plasma to about 20% of original level and that of 3,5,3'-triiodothyronine (T3) to about 60% of that was found, while the level of 3,3',5'-triiodothyronine (rT3) was increased 20%. It was concluded that the administration of salicylate results in an immediate displacement of T4 and T3 from plasma protein binding and possibly inhibits the conversion of T4 to T3 and of rT3 to 3,3'-diiodothyronine which results in an increase of rT3 level in plasma. This might by partially prevented by an inhibiting effect of salicylate on the binding of rT3 to plasma proteins.
PMID: 7298011 [PubMed - indexed for MEDLINE]
1: J Clin Endocrinol Metab. 1981 Mar;52(3):517-22. Links
Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man.
* Nishikawa M,
* Inada M,
* Naito K,
* Ishii H,
* Tanaka K,
* Mashio Y,
* Imura H.
To evaluate the effects of aging on T4 metabolism, serum 3,3'diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronine (3,5-T2) as well as T4, T3, and rT3 concentrations were determined by RIAs in 81 normal subjects, aged 24-81 yr. 3,3'-T2, 3',5'-T2, and 3,5-T2 antisera were prepared by immunizing rabbits with the protein conjugate of each diiodothyronine. Since the 3',5'-T2 antiserum cross-reacted with rT3 to the extent of 1.8%, correction was made by subtracting 1.8% of the rT3 value from the measured 3',5'-T2 value. The other 2 antisera had no noticeable cross-reactivity with various thyroid hormone derivatives. Although no significant relation existed between T4 levels and age (r = -0.14; P greater than 0.1) serum T3 showed a significant correlation with age (r = -0.28; P less than 0.05). In contrast, no significant correlation was observed between rT3 and age (r = 0.12; P greater than 0.1). Serum 3,3'-T2, 3',5'-Tw, and 3,5-T2 values (nanograms per dl) all had significant inverse correlations with age, the coefficients of correlation being -0.38 for 3,3'-T2 (P less than 0.01), -0.58 for 3',5'-Tw (P less than 0.01), and -0.47 for 3,5-T2 (P less than 0.01). These findings suggest that sequential monodeiodinating activities in T4 metabolism decrease with increasing age.
PMID: 7462404 [PubMed - indexed for MEDLINE]
The metabolism of 3,3'-diiodothyronine in man.
* Galeazzi RL,
* Burger AG.
The production rate of 3,3'-Diiodothyronine (3,3'-T2) was measured in five healthy subjects after a single injection of [125I]3,3'-T2. The [125I]3,3'-T2 was measured by immunoprecipitation. To reduce the large amount of nonspecific serum radioactivity (iodides, 3,3'-T2 metabolites, and protein-bound iodine), the sear were treated before the immunoprecipitation with an anion exchanger and polyethylene glycol (final concentration, 10%). The noncompartmental analysis of the data gave the following results: MCR, 0.52 +/- 0.07 liters/min or 926 +/- 142 liters/day (mean +/- SD); and production rate, 23.7 +/- 8.2 ng/min or 34 +/- 12 micrograms/day.
PMID: 6153081 [PubMed - indexed for MEDLINE]
1: Metabolism. 1978 Jun;27(6):677-83.Click here to read Links
Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation.
* Burman KD,
* Dimond RC,
* Djuh YY,
* Bruton J,
* Washburn TB,
* Wright FD,
* Wartofsky L.
In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.
PMID: 418309 [PubMed - indexed for MEDLINE]
More:
Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs.
* Verhoeven FA,
* Van der Putten HH,
* Hennemann G,
* Lamers JM,
* Visser TJ,
* Everts ME.
Department of Internal Medicine, Erasmus University Medical School, Rotterdam, The Netherlands.
Cellular and nuclear uptake of [125I]tri-iodothyronine (T3) and [125I]triiodothyroacetic acid (Triac) were compared in cardiomyocytes of 2-3 day old rats, and the effect of thyroid hormone analogs on cellular T(3) uptake was measured. Cells (5-10 x 10(5) per well) were cultured in DMEM-M199 with 5% horse serum and 5% FCS. Incubations were performed for from 15 min to 24 h at 37 degrees C in the same medium, 0.5% BSA and [125I]T3 (100 pM), or [125I]Triac (240 pM). Expressed as % dose, T(3) uptake was five times Triac uptake, but expressed as fmol/pM free hormone, Triac uptake was at least 30% (P<0.001) greater than T3 uptake, whereas the relative nuclear binding of the two tracers was comparable. The 15 min uptake of [125I]T3 was competitively inhibited by 10 microM unlabeled T3 (45-52%; P<0.001) or 3,3'- diiodothyronine (T2) (52%; P<0.001), and to a smaller extent by thyroxine (T(4)) (27%; 0.05We conclude that i) Triac is taken up by cardiomyocytes; ii) 3,3'-T2 and, to a lesser extent, DITPA and T4 interfere with plasma membrane transport of T3, whereas 3,5-T2, Triac, or Tetrac do not; iii) the transport mechanism for Triac is probably different from that for T3.
PMID: 12010632 [PubMed - indexed for MEDLINE]
3,3'-Diiodothyronine concentrations in the sera of patients with nonthyroidal illnesses and brain tumors and of healthy subjects during acute stress.
* Pinna G,
* Hiedra L,
* Meinhold H,
* Eravci M,
* Prengel H,
* Brodel O,
* Graf KJ,
* Stoltenburg-Didinger G,
* Bauer M,
* Baumgartner A.
Department of Radiology, Universitatsklinikum Benjamin Franklin, Free University of Berlin, Germany.
In this article we describe the development of a highly sensitive, accurate, and reproducible RIA for the measurement of 3,3'-diiodothyronine (3,3'-T2) in human serum and brain tissue. The detection limits were 1.8 fmol/g and 1.5 pmol/L in human brain tissue and serum, respectively. Serum concentrations of 3,3'-T2 were measured in 4 groups of patients with nonthyroidal illnesses (NTI), i.e. brain injuries (n = 15), sepsis (n = 24), liver disease (n = 22), and brain tumors (n = 23). The mean serum concentration of 3,3'-T2 in 62 healthy controls was 46.6 +/- 20.0 pmol/L. 3,3'-T2 levels declined significantly with increasing age. They were significantly lower in patients with brain injury (34.2 +/- 19.4 pmol/L; P = 0.006), were at the upper limit of normal in patients with sepsis (57.0 +/- 36.9 pmol/L; P = 0.06), and were elevated in patients with liver disease (72.6 +/- 56.7 pmol/L; P = 0.04) and brain tumors (89.0 +/- 40.9 pmol/L; P = 0.01). The serum levels of T3 were significantly lower than those in controls in all 4 patient groups. Serum concentrations of 3,3'-T2 were significantly enhanced in 9 patients with hyperthyroidism (85.4 +/- 43.0 pmol/L; P = 0.01) and were reduced in 12 patients with hypothyroidism (14.9 +/- 9.2 pmol/L; P = 0.001). In both normal brain tissue, obtained either intraoperatively or excised postmortem, and brain tumors, the concentrations of 3,3'-T2 ranged between 50-300 fmol/g. In healthy controls, 2 different forms of acute stress (sleep deprivation and delivering a lecture) significantly increased serum levels of T4 and T3, but did not affect those of 3,3'-T2 or 3,5-T2. In conclusion, our results show that, contrary to expectation, a low T3 syndrome in NTI is not always associated with low serum concentrations of 3,3'-T2. The production of 3,3'-T2 in NTI seems to be regulated in a disease-specific manner, resulting in unchanged, reduced, or elevated hormone concentrations.
PMID: 9745405 [PubMed - indexed for MEDLINE]
Effect of 3,5-diiodo-L-thyronine on thyroid stimulating hormone and growth hormone serum levels in hypothyroid rats.
* Moreno M,
* Lombardi A,
* Lombardi P,
* Goglia F,
* Lanni A.
Dipartimento di Chimica, Facolta di Scienze, Universita degli Studi di Salerno, Italy.
We have investigated the biological effects of physiological doses of 3,5-diiodo-L-thyronine (3,5-T2) and 3,3'-diiodo-L-thyronine (3,3'-T2) (at doses from 2.5 to 10 microg/100 g BW) on serum TSH and GH levels in rats made hypothyroid by propylthiouracil and iopanoic acid administration. In such animals deiodinase activities were inhibited and thyroid hormones serum levels strongly reduced. The effects of T2s were compared with those elicited by 3,5,3'-triiodo-L-thyronine (T3) (2.5 microg/100 g BW).The serum TSH level was much greater in hypothyroid rats than in euthyroid ones. T3 administration suppressed TSH by 88% compared to control (i.e, the level in hypothyroid rats); it thus reached a value not significantly different from that seen in the euthyroid rats. 3,5-T2 produced a similar effect, suppressing the TSH level by about 75% compared to control; it thus reached values not significantly different from those of the euthyroid and T3-treated rats. By contrast, 3,3'-T2 had no effect on TSH, whatever the dose. The serum GH level was much lower in hypothyroid rats than in euthyroid ones. T3 administration increased the GH level by about 5-fold, restoring it to the value seen in euthyroid rats. 3,5-T2-treated hypothyroid rats, at all the doses used (from 2.5 to 10 microg/100 g BW), showed increased serum GH levels: at a dose of 10 microg/100 g BW the level reached a value about 5-fold higher than that in hypothyroid rats. This value was not significantly different from those of euthyroid and T3-treated rats. 3,3'-T2 did not affect GH levels whatever the dose. Thus, 3,5-T2 (but not 3,3'-T2) seems to mimic the effects of T3 on serum TSH and GH levels in rats.
PMID: 9651103 [PubMed - indexed for MEDLINE]
Interaction of diiodothyronines with isolated cytochrome c oxidase.
* Goglia F,
* Lanni A,
* Barth J,
* Kadenbach B.
Dipartimento di Fisiologia Generale ed Ambientale, Universita degli Studi di Napoli Federico II, Italy.
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 (T3) 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.
PMID: 8013649 [PubMed - indexed for MEDLINE]
Effect of 3,3'-di-iodothyronine and 3,5-di-iodothyronine on rat liver mitochondria.
* Lanni A,
* Moreno M,
* Cioffi M,
* Goglia F.
Dipartimento di Fisiologia Generale ed Ambientale, Universita di Napoli, Italy.
In the present study we report that 3,3',5-tri-iodothyronine (T3) as well as two iodothyronines (3,5-di-iodothyronine (3,5-T2) and 3,3'-di-iodothyronine (3,3'-T2)) significantly influence rat liver mitochondrial activity. Liver oxidative capacity (measured as cytochrome oxidase activity/g wet tissue) in hypothyroid compared with normal rats was significantly reduced (21%, P > 0.01) and the administration of T3 and both iodothyronines restored normal values. At the mitochondrial level, treatment with T3 stimulated respiratory activity (state 4 and state 3) and did not influence cytochrome oxidase activity. On the other hand, both the mitochondrial respiratory rate and specific cytochrome oxidase activity significantly increased in hypothyroid animals after treatment with 3,3'-T2 or 3,5-T2 (about 50 and 40% respectively). The actions of both iodothyronines were rapid and evident by 1 h after the injection. The hepatic mitochondrial protein content which decreased in hypothyroid rats (9.6 mg/g liver compared with 14.1 in normal controls, P < 0.05) was restored by T3 injection, while neither T2 was able to restore it. Our results suggest that T3 and both iodothyronines have different mechanisms of action. T3 acts on both mitochondrial mass and activity; the action on mitochondrial activity was not exerted at the cytochrome oxidase complex level. The action of the iodothyronines, on the other hand, is exerted directly on the cytochrome oxidase complex without any noticeable action on the mitochondrial mass.
PMID: 8381457 [PubMed - indexed for MEDLINE]
Effect of 3,3'-diiodothyronine and 3,5-diiodothyronine on rat liver oxidative capacity.
* Lanni A,
* Moreno M,
* Cioffi M,
* Goglia F.
Department of General and Environmental Physiology, University of Naples, Italy.
We report that 3,5,3'-triiodothyronine (T3) as well as two other iodothyronines (3,3'-diiodothyronine and 3,5-diiodothyronine (T2s)) stimulate rat liver oxidative capacity (measured as cytochrome oxidase activity (COX)). In hypothyroid rats COX activity and mitochondrial protein content are significantly lower than in normal control animals. The administration of both T3 and T2s to hypothyroid rats significantly enhances hepatic COX activity with T3 having the greatest effect (+60%); moreover, T3 restores the mitochondrial protein content whereas the T2s are ineffective. Administration of T2s results in a faster stimulation (already significant 1 h after the injection) of hepatic COX activity than T3 injection. Our results suggest that T3 acts on the protein synthesis mechanism involved in the regulation of the mitochondrial mass while T2s would act directly at the mitochondrial level.
PMID: 1324858 [PubMed - indexed for MEDLINE]
Serum concentrations of 3, 3'-diiodothyronine, 3', 5'-diiodothyronine, and 3, 5-diiodothyronine in altered thyroid states.
* Nishikawa M,
* Inada M,
* Naito K,
* Ishii H,
* Tanaka K,
* Mashio Y,
* Imura H.
To investigate the thyroid hormone metabolism in altered states of thyroid function, serum concentrations of 3, 3'-diiodothyronine (3, 3'-T2), 3', 5'-T2 and 3, 5-T2 as well as T4, T3 and rT3 were determined by specific radioimmunoassays in 17 hyperthyroid and 10 hypothyroid patients, before and during the treatment. Serum T4, T3, rT3, 3, 3'-T2 and 3', 5'-T2 concentrations were all higher in the hyperthyroid patients than in age-matched controls and decreased to the normal ranges within 3 to 4 months following treatment with antithyroid drugs. In the hypothyroid patients, these iodothyronine concentrations were lower than in age-matched controls and returned to the normal ranges after 2 to 3 months treatment with T4. In contrast, serum 3, 5-T2 concentrations in hyperthyroid patients (mean +/- SE : 4.0 +/- 0.5 ng/dl) were not significantly different from those in controls (3.9 +/ 0.4 ng/dl), although they tended to decrease in 3 of 6 patients after the antithyroid drug therapy. Serum 3, 5-T2 levels in the hypothyroid patients (3.8 +/- 0.6 ng/dl) were also within the normal range and showed no significant change following the T4 replacement therapy. However, serum 3, 5-T2 as well as 3, 3'T2 concentrations rose significantly with a marked rise in serum T3 following T3 administration, 75 micrograms/day for 7 days, in Graves' patients in euthyroid state.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 6641638 [PubMed - indexed for MEDLINE]
Immediate opposite effect of salicylate on thyroxine and 3,5,3'-triiodothyronine versus 3,3',5'-triiodothyronine level in plasma in rats.
* Langer P,
* Foldes O,
* Brozmanova H,
* Straussova K,
* Gschwendtova K.
In a total of 46 male rats polyethylene tubings were introduced into femoral artery and vein under pentobarbiturate anesthesia. Then heparin (300 U kg-1) was injected at 60-90 min after pentobarbiturate and two control blood samples were subsequently taken. After that sodium salicylate (200 mg kg-1) was injected i.v. and blood samples were taken at 30-420 min later. An immediate decrease of the thyroxine (T4) level in plasma to about 20% of original level and that of 3,5,3'-triiodothyronine (T3) to about 60% of that was found, while the level of 3,3',5'-triiodothyronine (rT3) was increased 20%. It was concluded that the administration of salicylate results in an immediate displacement of T4 and T3 from plasma protein binding and possibly inhibits the conversion of T4 to T3 and of rT3 to 3,3'-diiodothyronine which results in an increase of rT3 level in plasma. This might by partially prevented by an inhibiting effect of salicylate on the binding of rT3 to plasma proteins.
PMID: 7298011 [PubMed - indexed for MEDLINE]
1: J Clin Endocrinol Metab. 1981 Mar;52(3):517-22. Links
Age-related changes of serum 3,3'-diiodothyronine, 3',5'-diiodothyronine, and 3,5-diiodothyronine concentrations in man.
* Nishikawa M,
* Inada M,
* Naito K,
* Ishii H,
* Tanaka K,
* Mashio Y,
* Imura H.
To evaluate the effects of aging on T4 metabolism, serum 3,3'diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronine (3,5-T2) as well as T4, T3, and rT3 concentrations were determined by RIAs in 81 normal subjects, aged 24-81 yr. 3,3'-T2, 3',5'-T2, and 3,5-T2 antisera were prepared by immunizing rabbits with the protein conjugate of each diiodothyronine. Since the 3',5'-T2 antiserum cross-reacted with rT3 to the extent of 1.8%, correction was made by subtracting 1.8% of the rT3 value from the measured 3',5'-T2 value. The other 2 antisera had no noticeable cross-reactivity with various thyroid hormone derivatives. Although no significant relation existed between T4 levels and age (r = -0.14; P greater than 0.1) serum T3 showed a significant correlation with age (r = -0.28; P less than 0.05). In contrast, no significant correlation was observed between rT3 and age (r = 0.12; P greater than 0.1). Serum 3,3'-T2, 3',5'-Tw, and 3,5-T2 values (nanograms per dl) all had significant inverse correlations with age, the coefficients of correlation being -0.38 for 3,3'-T2 (P less than 0.01), -0.58 for 3',5'-Tw (P less than 0.01), and -0.47 for 3,5-T2 (P less than 0.01). These findings suggest that sequential monodeiodinating activities in T4 metabolism decrease with increasing age.
PMID: 7462404 [PubMed - indexed for MEDLINE]
The metabolism of 3,3'-diiodothyronine in man.
* Galeazzi RL,
* Burger AG.
The production rate of 3,3'-Diiodothyronine (3,3'-T2) was measured in five healthy subjects after a single injection of [125I]3,3'-T2. The [125I]3,3'-T2 was measured by immunoprecipitation. To reduce the large amount of nonspecific serum radioactivity (iodides, 3,3'-T2 metabolites, and protein-bound iodine), the sear were treated before the immunoprecipitation with an anion exchanger and polyethylene glycol (final concentration, 10%). The noncompartmental analysis of the data gave the following results: MCR, 0.52 +/- 0.07 liters/min or 926 +/- 142 liters/day (mean +/- SD); and production rate, 23.7 +/- 8.2 ng/min or 34 +/- 12 micrograms/day.
PMID: 6153081 [PubMed - indexed for MEDLINE]
