Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

Yu, Shu-Guang; Friedman, Yochanan; Richman, Robert A.; Burke, Gerald

doi:10.1172/jci108333

Cited by 59 publications

(16 citation statements)

References 20 publications

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“…Release of T4, T3, or iodide induced by TSH might contribute to the refractoriness related to organification of iodide. Such a short-loop feedback system has been reported both in vivo and in vitro (13)(14)(15) but has also been denied in vivo (16). In the present experiments, thyroid hormones did not diminish the TSH stimulation of organification of iodide (Fig.…”

Section: Resultssupporting

confidence: 61%

“…3). Although the amount of T3 and T4 used in the present experiments was less than that which inhibited cyclic AMP generation in the in vitro experiments of Yu et al (13), the concentration used in the present experiments is still supraphysiologic and is similar to what we have used previously (1). In the latter experiments T3 and T4 did not modify the effect of TSH on generation of cyclic AMP.…”

Section: Resultssupporting

confidence: 55%

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

Field¹,

Dekker²,

Titus³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and 32Pi incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E1 were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 ,uM thyroxine or triiodothyronine or 1.5 ,M iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1 mM iodide in the buffer during all three incubations inhibited the response to TSH during the third incubation. During the refractory period, effects of TSH on colloid droplet formation were also diminished. The in vivo effect of TSH on serum 1-triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by unresponsiveness of adenylate cyclase because effects of dibutyryl cyclic AMP and prostagladin E1 were also inhibited by prior exposure to TSH.

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Section: Resultssupporting

confidence: 61%

Section: Resultssupporting

confidence: 55%

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

Field¹,

Dekker²,

Titus³

et al. 1979

J. Clin. Invest.

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“…Serum levels of T3 and T4 were much higher than those of MTU-controls on these days. These data together with observations of Yu et al (1976) that the pretreatment of rats and mice with T3 or T4 blunted the induction of thyroid ODC activity by exogenous TSH, suggest that circulating thyroid hormones may act directly on the thyroid to depress the response of thyroid ODC to TSH.…”

Section: Discussionmentioning

confidence: 59%

Thyroid function and polyamines. III. Changes in ornithine decarboxylase activity and polyamine contents in the rat thyroid during hyperplasia and involuton.

et al. 1978

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SynopsisChanges in ornithine decarboxylase (ODC) activity and in polyamine contents of the rat thyroid were studied under various experimental conditions. Methylthiouracil (MTU) treatment produced several-fold increases in the thyroid ODC activity and in the content of putrescine, spermidine and spermine within a week. While serum thyrotropin (TSH) levels increased gradually up to 3 weeks, the content of both putrescine and spermidine tended to reach a plateau after 2 weeks of the goitrogen treatment;spermine content continued to increase progressively for 3 weeks. Discontinuance of MTU at 7 days resulted in a rapid decline in the elevated thyroid ODC activity, followed by a diminution of putrescine, spermidine and RNA contents. Thyroidal putrescine, spermidine and RNA responded more sensitively to both introduction and withdrawal of TSH stimulation than thyroidal spermine and DNA.Excess iodide, having no effect on the basal level of thyroid ODC, suppressed the MTU-induced increase in this enzyme activity without affecting circulating TSH, thyroxine (T4) and triiodothyronine (T3) levels. There was a significant negative correlation between the ODC activity and intrathyroidal concentration of iodine in MTUpretreated rats. Theophylline increased the thyroid weight and ODC activity when given to rats fed with a subeffective dose of MTU. Analyses of serum TSH, T4, T3 and of thyroidal iodine revealed that TSH-induced thyroid ODC activity was suppressed by increased circulating thyroid hormones and/or intrathyroidal iodine. Furthermore, it was suggested that thyroid hormones and excess iodide acted directly on the thyroid to alter polyamine biosynthesis, possibly by changing the responsiveness of the gland to TSH.The polyamines, spermidine and spermine and their precursor putrescine, occur ubiquitously in living organisms. The fact that polyamines are found at high concentrations in rapidly growing tissues suggests that these biogenic amines play an important role in the regulation of growth processes (

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“…Finally, concentrationis of T3 -(100-fold higher than those required to enhanee 2-DG uiptake in thymocytes are necessary to produce inhibition of the adenylate cyclase response to exogenous thyrotropin by bovine thyroid membranes. The concentration of T3 required for the latter effect (50 ,M) is about six orders of magnitude greater than the presumed free T3 concentration in vivo; nevertheless, a seemingly similar inhibition of thyroid a(lenylate cyclase response to exogenous thyrotropin could be produced by the administration of only 2.5 ,ug of T3 to the mouse (53,54).…”

Section: Discussionmentioning

confidence: 94%

Stimulation by Triiodothyronine of the In Vitro Uptake of Sugars by Rat Thymocytes

Segal¹,

Ingbar²

1979

J. Clin. Invest.

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A B S T R A C T Studies were conducted to ascertain the in vitro effect of 3,5,3'-triiodothyronine (T3) on the accumulation of the glucose analogue, 2-deoxyglucose (2-DG), by thymocytes freshly isolated from weanling rats. At a concentration of 1 ,uM, T3 stimulated the 15-min uptake of 3H-2-DG after cells had been exposed to T3 for only 30 min. Significant stimulation of 2-DG accumulation was produced by 1 nM T3, with increasing stimulation at doses ranging up to 10 ,uM. T3 did not alter the fraction of accumulated 2-DG that was phosphorylated, and kinetic studies indicated that its effect was associated with a significant increase in the apparent Vmax of 2-DG accumulation, but not the apparent Km. T3 also enhanced the accumulation by thymocytes of the nonmetabolized glucose analogue, 3-0-methylglucose (3-0-MG), an effect that was evidently the result of an increase in 3-0-MG transport into the cell, because it was seen in cells incubated with 3H-3-O-MG for only 30 s. The proportionate increase in 2-DG accumulation produced by T3 was not altered by preincubating cells with concentrations of puromycin or cycloheximide sufficient to reduce [3H]-leucine incorporation by 95%, and T3 over a period of >2 h had no effect on [3H]leucine incorporation itself.These results indicate that T3 stimulates the uptake of sugars in rat thymocytes in vitro by an effect on their inward transport. The promptness of the effect and its failure to be inhibited during profound inhibition of protein synthesis further indicate that this effect of T3 is not mediated through a nuclear-dependent mechanism. Rather, the properties of this response, and of the increases in amino acid and 2-DG accumulation produced by T3 in other tissue preparations, strongly suggest that these effects of T3 are mediated at the level of cell membrane.

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Altered thyroidal responsivity to thyrotropin induced by circulating thyroid hormones. A "short-loop" regulatory mechanism?

Cited by 59 publications

References 20 publications

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

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

Thyroid function and polyamines. III. Changes in ornithine decarboxylase activity and polyamine contents in the rat thyroid during hyperplasia and involuton.

Stimulation by Triiodothyronine of the In Vitro Uptake of Sugars by Rat Thymocytes

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