Disposal Rates of Thyroxine and Triiodothyronine in Iodine-Deficient Rats

Silva, Enrique

doi:10.1210/endo-91-6-1430

Cited by 32 publications

(9 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be argued that such animals are, by definition, hypothyroid. Nevertheless, as previously pointed out, they appear to be "clinically" euthyroid (2)(3)(4) (14). The fact that acute labeling with 'I results in the same Ts/T4 ratios as the immunoassay determination indicates that, in spite of the functional heterogeneity of thyroid gland iodine previously shown by many investigators, the Ts/T4 ratio of acutely formed hormone and total thyroidal iodothyronine are essentially the same.…”

Section: Analysis Of Data Inmentioning

confidence: 57%

“…Although Studer and Greer, and Greer, Grimm, and Studer have demonstrated that serum PBI decreases to very low levels within 1 mo of initiation of a low-iodine diet, rats maintained on this regimen for even 1 yr re-main healthy and grow at normal rates (2,3). Recent studies by Silva have shown that 02 con1Sumnption and body temperature regulation of rats under severe iodine restriction for 120 days is not different from that of control animals (4).…”

Section: Introductionmentioning

confidence: 98%

“…Mean serum T4 concentration in the control rats was 4.2±0.6 (SD) Ag T4/100 ml, 4.5+0. 3 Ag/100 ml in group B animals, and undectectable (<0.5 tL/100 ml) in group C animals.…”

mentioning

confidence: 93%

See 2 more Smart Citations

Triiodothyronine and Thyroxine in the Serum and Thyroid Glands of Iodine-Deficient Rats

Abrams¹,

Larsen²

1973

J. Clin. Invest.

153

View full text Add to dashboard Cite

A B S T R A C T Triiodothyronine (T3) and thyroxine (T4) were measured by immunoassay in the serum and thyroid hydrolysates of control (group A), mildly iodine-deficient (group B), and severely iodine-deficient rats (group C). These results were correlated with changes in thyroidal weight, 'I uptake and "2I content as well as with the distribution of 131I in Pronase digests of the thyroid. There was a progressive increase in thyroid weight and '1I uptake at 24 h with decrease in iodine intake. The PI content of the thyroids of the group B animals was 44% and that of the group C animals 2% of that in group A. The mean labeled monoiodotyrosine/diiodotyrosine (MIT/DIT) and T3/T4 ratios in group A were 0.42±0.07 (SD) and 0.12±0.01, 0.59±0.06 and 0.11±0.03 in group B, and 2.0±0.3 and 1.8±0.9 in the group thyroid digests.Mean serum T4 concentration in the control rats was 4.2±0.6 (SD) Ag T4/100 ml, 4.5+0.3 Ag/100 ml in group B animals, and undectectable (<0.5 tL/100 ml) in group C animals. There was no effect of iodine deficiency on serum T3 concentrations, which were 44+ 9 (Mean±SD) ng/100 ml in A animals, 48±6 ng/100 ml .n B animals, and 43+6 ng/100 ml in the C group. Thyroidal digest Ts and To concentrations were 39 and 400 ng/mg in group A animals and were reduced to 5 and 1% of this, respectively, in group C. The molar ratio of Ta/Ti in the thyroid digests of the groups A and B animals was identical to the ratio of labeled Ts/T4 and was slightly less (1.0±0.9) than the labeled T3/T ratio in the group C animals. T4/T3 ratio in the serum of each iodine-deficient animal. This analysis suggested that the labeled thyroid hormones in the severely iodine-deficient rat were secreted in the ratio in which they are present in the gland.Kinetic analysis of total iodothyronine turnover indicated that two-thirds of the Ts utilized per day by the iodine-sufficient rat arises from T4. If the Tr-Ts conversion ratio remains the same in iodine deficiency, then the analysis suggests that about 90% of the T3 arises directly from the thyroid. Therefore, it would appear that absolute Ts secretion by the thyroid increases severalfold during iodine deficiency. The fact that serum T3 remains constant and T4 decreases to extremely low levels, combined with previous observations that iodinedeficient animals appear to be euthyroid, is compatible with the hypothesis that T4 in the normal rat serves primarily as a precursor of T3. INTRODUCTIONThe thyroidal response to iodine deficiency has been an area of active investigation for many years. Previous studies in the rat reviewed by Studer and Greer indicate that when iodine intake is severely restricted there is an increase in thyroid weight, a decrease in protein-bound iodine (PBI)1 and an altered pattern of tracer iodine distribution in the thyroid gland (1). The last-mentioned changes include an increase in labeled monoiodotyrosine (MIT) and decrease in labeled diiodotyrosine (DIT) as well as a progressive increase in the ratio of labeled triiodothyronine (T3) to labeled thyroxine (T4). ...

show abstract

Section: Analysis Of Data Inmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Triiodothyronine and Thyroxine in the Serum and Thyroid Glands of Iodine-Deficient Rats

Abrams¹,

Larsen²

1973

J. Clin. Invest.

153

View full text Add to dashboard Cite

show abstract

“…There is a delay in the attainment of the peak T3 production rate by approximately 12 days. Assuming that the metabolic clearance rates of Tq and T3 are similar in iodine-deficient and iodinereplete animals (Silva 1972), the higher serum T3 concentrations seen in the LID animals after birth compared with controls (Table 2 ) suggest preferential production of T3.…”

Section: Discussionmentioning

confidence: 99%

The effect of iodine deficiency and propylthiouracil on the hypothalamo–pituitary–thyroid axis in the neonatal rat

Dussault¹,

Walker²

1978

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

D u s s a u~~, J. H., and WALKER, P. 1978. The effect of iodine deficiency and propylthiouracil on the hypothalarno-pituitary-thyroid axis in the neonatal rat. Can. J. Physiol. Pharmacol. 56,[950][951][952][953][954][955] The efTect of chronic propylthiouracil (PTU) and low iodide diet (LID) on the development of the hypothala~no-pituitary-thyroid axis in the rat has been studied. Pregnant and neonatal rats received 0.05% PTU in their drinking water or LID (distilled water and LID: Teklad Mills, Madison, Wisconsin). Colltrol animals received tap water and Purina rat chow ad libitum. Hypothalamic thyrotropin-releasing hormone (TRH), pituitary and serum thyroid-stimulating hormone (THS), and serum thyroxine (T4) and triiodothyronine (T,) were measured by specific double-antibody radioimmunoassay. Both PTU-and LID-exposed animals had low hypothalamic TRH concentrations at 1 day and a rapid rise to peak levels of 2.4 +-0.4 pg/,ug protein (mean zk SEM) between 12 and 24 days in the PTU animals and 3.2 ?z 0.4 pg/pg protein between 12 and 18 days in the LID rats. Hypothalamic TRH concentrations remained relatively stable in the BTU animals, whereas in the LID rats, after a brief but significant decline from 24 to 28 days, hypothalamic TRH concentrations rose to the highest values observed at 57 days (3.9 0.5 p p~/~g protein). Both groups of a~limals had elevated serum TSM levels at 1 day, with higher values seen in the PTU group (p < 0.01), and both showed a rapid rise at 12 days. Thereafter, serum TSH concentrations remained high in the PTU rats but declined to stable. albeit elevated, levels by 24 days (1260 9 140 ng/ml) in the LID animals.Hypothyroidism was confirmed in the PTU animals by undetectable T4 and reduced Ta concentrations. In the &I%$ rats, serum Ti concentrations rose from undetectable levels at 1 day to stable values by 32 days (2.18 & 0.13 ,ug/dl). Serum T, rose to peak values of 157.0 6.9 ng/dl at 32 days and was elevatcd at all times after 12 days. These data suggest that chronic exposure to PTU or I,ID resarlts in a anarked derangement of the ontogenetic pattern of the hypothalamo-pituitary-thyroid axis. In addition. neonatal rats exposed to LID appear to respond appropriately by preferential Ta production. DUSSAUET, J. H., et WALKER. P. 1978. The effect of iodine deficiency and propylthiouracil om the hypsthalamo-pituitasy-thyroid ,axis in the neonatal rat. Can. J. Physiol. Pharnmacol. 56,950-955. Om a ktudiC I'effet du PTU chronique et celui d'um dikte faible en isde (LID) sur le dCveloppement de I'axe hypothalomo-pituitairien-thyroidien du rat. Des rates gravides et des rats nouveau-nis ont requ 0.05% PTU dans leur eau de consommation ou dans leur LID (eau distillte et LID : Teklad Mills, Madison, Wisconsin). Les rats tkmoins ont r e p h volontC de l'eau du robinet et de la nourriture pour rat Purina. Le TRH hypothalamique, les TSH pituitaire et sCrique ainsi que les T, et Tg striques, ont kt6 mesurts par des dosages spicifiques radioimmunologiques. Ees rats nourris au PTU et au LID ont naontrC ...

show abstract

“…Our present studies suggest that the contribution of T4 to nuclear T3 in the liver and kidney is so small that significant nuclear desaturation would not occur in these tissues as a result of a modest decrease in plasma T4 alone. This could explain the circumstances in the iodine-deficient rat where an apparently euthyroid state is associated with a low plasma T4, normal plasma T3, and an elevated TSH (17,43). Similar arguments can be applied to explain why patients with endemic goiter, a high plasma TSH, and normal plasma T3 can appear euthyroid as well as why patients with early thyroid dysfunction with reduced plasma T4, normal plasma T3, and elevated TSH are often asvmptomatic in metabolic terms (44)(45)(46)(47).…”

Section: Specific Experimetital Protocolsmentioning

confidence: 89%

Contributions of Plasma Triiodothyronine and Local Thyroxine Monodeiodination to Triiodothyronine to Nuclear Triiodothyronine Receptor Saturation in Pituitary, Liver, and Kidney of Hypothyroid Rats

Silva¹,

Larsen²

1978

J. Clin. Invest.

209

View full text Add to dashboard Cite

A B S T R A C T Inijections of triiodothyronine (T3)and thyroxine (T4) into chronically hypothyroid rats were used to evaluate the contribution of intracellular T4 to T3 conversion to nuclear T3 in pituitary, liver, and kidney, and to correlate the occupancy of pituitary nuclear T3 receptors with inhibition of thyroid-stimulating hormone (TSH) release. Injection of a combination of 70 ng T3 and 400 ng T4/100 g body wt resulted in plasma T3 concentrations of 45+7 ng/dl (mean±+-SD) and 3.0±0.4,ug/dl T43 h later. At that plasma T3 level, the contribution of plasma T3 to the nuclear receptor sites resulted in saturation of 34±7% for pituitary, 27±5% for liver, and 33+2% for kidney. In addition to the T3 derived from plasma T3, there was additional T3 derived from intracellular monodeiodination of T4 in all three tissues that resulted in total nuclear occuipancy (as percent saturation) of 58±11% (pituitary), 36±8% (liver), and 41+11% (kidney), respectively. The percent contribution of T3 derived from cellular T4 added 41% of the total nuclear T3 in the pituitary which was significantly higher than the contribution of this source in the liver (24%) or the kidney (19%). 3 h after intravenous injection of increasing doses of T3, the plasma T3 concentration correlated well with both the change in TSH and the nuclear occupancy, suggesting a linear relationship between the integrated nuclear occupancy by T3 and TSH release rate. The contribution of intrapituitary T4 to T3 conversion to nuclear T, was accompanied by an appropriate decrease in TSH, supporting the biological relevance of nuclear T3. Pretreatment of the animals with 6-n-propylthiouracil before T4 injection decreased neither the nuclear T3 derived from intrapituitary T4 nor the subsequent decrease in TSH.These results indicate that intracellular monodeiodination of T4 contributes substantially to the nuclear T3 in the pituitary of the hypothyroid rat, and suggest a linear inverse relationship between nuclear receptor occupancy by T3 in the pituitary and TSH release rate. The data further indicate that T4 to T3 monodeiodination is considerably more important as a source of nuclear T3 in the pituitary than in the liver and kidney. This provides a mechanism whereby the TSH secretion could respond promptly to a decrease in thyroid secretion (predominantly T4) before a decrease in plasma T3 would be expected to lead to significant metabolic hypothyroidism. INTRODUCTIONThere is considerable indirect evidence suggesting that interaction of triiodothyronine (T3)l with a specific

show abstract

Disposal Rates of Thyroxine and Triiodothyronine in Iodine-Deficient Rats

Cited by 32 publications

References 1 publication

Triiodothyronine and Thyroxine in the Serum and Thyroid Glands of Iodine-Deficient Rats

Triiodothyronine and Thyroxine in the Serum and Thyroid Glands of Iodine-Deficient Rats

The effect of iodine deficiency and propylthiouracil on the hypothalamo–pituitary–thyroid axis in the neonatal rat

Contributions of Plasma Triiodothyronine and Local Thyroxine Monodeiodination to Triiodothyronine to Nuclear Triiodothyronine Receptor Saturation in Pituitary, Liver, and Kidney of Hypothyroid Rats

Contact Info

Product

Resources

About