In Vitro and In Vivo Refractoriness to Thyrotropin Stimulation of Iodine Organification and Thyroid Hormone Secretion

Field, James B.; Dekker, Andrew; Titus, Gail; Kerins, Mary E.; Worden, William; Frumess, Rosalyn

doi:10.1172/jci109447

Cited by 26 publications

(9 citation statements)

References 19 publications

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“…This occurred in PTUand LID-treated animals, but much less so in animals FIGURE 2 Thyroid depletion and repletion in "continuously" TSH treated rats. Thyroid sections of a control rat (A) and ofrats injected with 1 IU TSH at 8-h intervals over 1 (B) and 4 (27). The paper reviews the available literature up to 1977.…”

Section: Introductionmentioning

confidence: 99%

Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.

Gerber¹,

Studer²,

Conti³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Since Marine's observations some 50 years ago, it has been generally accepted that colloid goiters invariably result from colloid repletion of originally hyperplastic goiters after cessation of the goitrogenic stimulus. However, clinical observations suggest that many goiters never go through a stage of hyperplasia, but are colloid-rich from the beginning.We have injected rats and mice with thyrotropin (TSH), three times a day for 4 d, while the animals were kept on an iodine-rich diet (HID). Additional groups of animals were fed an iodine-poor diet (LID) or a diet containing 0.15% propylthiouracil (PTU) or 1% sodium perchlorate (C104). At intervals, thyroid weight, DNA, iodine and thyroglobulin content, thyroglobulin iodination, and intracellular droplet formation were measured. Histologic sections were also prepared and stained with periodic acid Schiff. Furthermore, thyroxine concentration was measured in the serum.Thyroglobulin content dropped by -30% in HID animals but by 60% in all other groups 1 d after starting TSH. Thereafter, thyroglobulin reaccumulation occurred and droplet formation correspondingly decreased despite continuous heavy TSH stimulation. The largest amount ofthyroglobulin was reaccumulated in HID animals followed by the PTU/LID groups, whereas no reaccumulation was observed in the C104 group. Reaccumulation of thyroglobulin only occurred if there was concomitant organification of at least some iodine. The subsequent phases of depletion and re-

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Section: Introductionmentioning

confidence: 99%

Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.

Gerber¹,

Studer²,

Conti³

et al. 1981

J. Clin. Invest.

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“…Several in vitro studies have been reported show¬ ing that prior exposure to TSH induces refractori¬ ness to further hormonal stimulation. This pheno¬ menon was demonstrated using slices from dog, bovine and human (Field et al 1979) (Takasu et al 1978) thyroid cells in culture. It is probable that such a refractoriness has also developed after expo¬ sure of our thyroid cells to TSH.…”

Section: Discussionmentioning

confidence: 86%

Some unexpected effects of thyrotrophin on the metabolism of thyroid cells isolated from non-toxic goitre

Wadeleux

Winand

1981

Acta Endocrinologica

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In cultured cells of normal dog thyroid, thyrotrophin (TSH) has been shown to have a mitogenic effect. The present study suggests an opposite action in cells from human non-toxic goitre. After incubation of these cells with [3H]thymidine, a decreased incorporation into DNA is observed in the presence of TSH.Whereas in dog thyroid cells the hormone enhances the incorporation of [3H]leucine and [14C]glucosamine into macromolecules, TSH inhibits the incorporation by human non-toxic goitre cells. Polyacrylamide gel electrophoresis analysis of the proteins present in the cell layer or released in the culture medium shows that the inhibition affects all the newly synthesized peptides, including the radioactive material co-migrating with the major band (330000 daltons) observed with human purified thyroglobulin.While several hydrolase activities are not influenced by TSH in dog thyroid cells, the hormone markedly decreases the activities of some hydrolases of thyroid cells from human non-toxic goitre. Our results therefore suggest that, in cultured thyroid cells from human non-toxic goitre, TSH induces a resting state of the cells, characterized by reduced growth, reduced protein synthesis and reduced thyroglobulin hydrolysis.As recently reviewed by Studer et al. (1979), there seems to be no qualitative abnormality of thyroid function in the large majority of polynodular spo¬ radic goitres; the development of these goitres seems to be caused by disturbances in the coordina¬ tion of some processes responsible for normal thyroid structure and function, disturbances in which TSH is believed to play a key role.Previous studies using primary cultures of thy¬ roid cells isolated from non-toxic goitre showed that they were sensitive to TSH stimulation, as shown by the increase in cyclic AMP (Lee et al.

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“…It is well known that chronic TSH treatment causes thyroid desensitizatioo to subsequent TSH stimulation in vivo as well as in vitro (Rapoport & Adams 1976;Field et al 1979;Zakarija & McKenzie 1975;Holmes et al 1980). In the present study, TSH was injected daily for 3-4 days.…”

Section: Discussionmentioning

confidence: 99%

Tonic effect of endogenous TSH on the in vitro thyroid cAMP response to TSH

Ikeda

Uchimura

Nagataki

1984

Acta Endocrinologica

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The present study was undertaken to compare the effects of 3,5,3'-triiodothyronine (T3) alone and T3 plus bovine thyrotrophin (bTSH) given chronically in vivo on the TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in a mouse thyroid in vitro. Mice were given T3 (5 \g=m\g/ml) in drinking water for 4 days. The thyroid cAMP concentrations after an incubation with 10 mU/ml of TSH for 10 min were decreased by 50% in T3-treated mice as compared to the control. In the second experiment, mice were given T3 alone or T3 plus 0.5 mU of bTSH ip daily for 4 days. The combined treatment with T3 and TSH partially restored the reduction of cAMP response to TSH that was induced by T3 alone. In the third experiment, mice were given T3 alone for 7 days, or T3 for 7 days plus TSH for the last 3 days. The reduced cAMP response to TSH induced by T3 alone was again partially restored by the concomitant treatment with TSH.These results indicate 1) that the capacity of the thyroid cAMP to respond to TSH is regulated, at least in part, by a trophic effect of endogenous TSH and 2) that the impaired capacity caused by a loss of tonic effect of endogenous TSH is reversible.It has been well documented that in vivo admini¬ stration of thyroid hormone to animals causes a decrease in the capacity of the thyroid gland to respond to thyrotrophin (TSH) (Croxson et al.

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In Vitro and In Vivo Refractoriness to Thyrotropin Stimulation of Iodine Organification and Thyroid Hormone Secretion

Cited by 26 publications

References 19 publications

Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.

Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.

Some unexpected effects of thyrotrophin on the metabolism of thyroid cells isolated from non-toxic goitre

Tonic effect of endogenous TSH on the in vitro thyroid cAMP response to TSH

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