Limited Binding Capacity Sites for l-Triiodothyronine in Rat Liver Nuclei

Oppenheimer, Jack H.; Schwartz, Harold L.; Koerner, Diona R.; Surks, Martin I.

doi:10.1172/jci107615

Cited by 167 publications

(49 citation statements)

References 21 publications

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“…This correspondence supports our assumptions about the role of free T3 in the equilibration of hormone between cells, nuclei, and medium. Furthermore, the binding capacity per cell in six experiments was 12,000+3,000 sites (SD) or 0.68 ng T3/mg DNA, a value similar to that previously found in whole liver homogenates, 0.6 ng/mg DNA (14). We and 500-mg/dl glucose concentrations was -10 h (Fig.…”

Section: Resultssupporting

confidence: 85%

Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal.

Mariash¹,

McSwigan²,

Towle³

et al. 1981

J. Clin. Invest.

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A B S T R A C T We have simulated in a cultured hepatocyte system the synergistic interaction between triiodothyronine (T3) and dietary carbohydrate in the induction of malic enzyme (ME). Kinetic studies revealed that isolated hepatocytes equilibrate with media T3 within 5 min; nuclei equilibrate with media T3 by 45 min; and the half-time of T3 metabolism was 10 h in 10% serum. We demonstrated nuclear T3 receptors in isolated hepatocytes and the induction of ME by T3 in physiological concentrations. However, in the complete absence of T3 glucose could still induce ME. At all concentrations of glucose (100-1,000 mg/dl), T3 (0.3 nM free T3) resulted in a relatively constant (1.4-to 1.7-fold) increase in ME response. The augmentation in ME activity was paralleled by an enhanced rate of enzyme synthesis as determined by [3H]leucine incorporation into immunoprecipitable ME. Cells cultured in serum free media also demonstrated a glucose-dependent increase in ME. Insulin greatly stimulated the glucose induction of ME, whereas dexamethasone had very little influence on ME induction. These studies demonstrate the usefulness of an adult hepatocyte tissue culture model for the study of the effects of T3 on gene expression in cells that are not derived from tumor. They clearly demonstrate that well established effects of T3 can be simulated in such a system at levels of free hormone that approximate those in extracellular body fluids. Our results indicate that an increased concentration of glucose per se can induce the formation of ME in the absence of alterations in extrahepatic hormones or factors. Moreover, our findings confirm inferences from in vivo studies that T3 acts as a multiplier of a glucoseinduced signal.

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Section: Resultssupporting

confidence: 85%

Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal.

Mariash¹,

McSwigan²,

Towle³

et al. 1981

J. Clin. Invest.

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“…Similar observations have also been made on thyroid hormone binding in rat liver by Oppenheimer and his coworkers (10)(11)(12) and more recently by several other investigators (13)(14)(15).…”

supporting

confidence: 82%

“…A primary injection of 50014g of purified rat growth hormone, dissolved in 5 mM NaOH, was administered with an equal volume of Freund's adjuvant by subcutaneous injection. This procedure was repeated at 3-to 4-week intervals, and [10][11][12] days after the previous immunization 200 ml of blood was collected into 40 ml of citrate-dextrose solution to prevent clotting as described by Bancroft (16). The antigrowth hormone plasma obtained was stored at -20°.…”

mentioning

confidence: 99%

Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process.

Samuels¹,

Shapiro²

1976

Proc. Natl. Acad. Sci. U.S.A.

145

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We have previously demonstrated with radioimmunoassay techniques that physiologic concentrations of thyroid hormone stimulate an increase in growth hormone production in GH, cells in culture. In this study, with radiolabel techniques and selective immunoprecipitation, we demonstrate that Ltriiodothyronine stimulates growth hormone production solely by inducing an increase in the de novo synthesis of the polypeptide hormone. L-Triiodothyronine stimulated synthetic rates of growth hormone by 1.5-fold in 1.25 hr, 2-fold in 2.5 hr, to a maximal of 3-to 4-fold after 8.5 hr of incubation. The time interval between significant L-triiodothyronine binding to putative nuclear receptors and a detectable increase in growth hormone synthesis was 45-60 min.Studies on the effect of actinomycin D, 3'-deoxyadenosine, and cycloheximide support the thesis that L-triiodothyronine induces the accumulation of an RNA species which is rate limiting for growth hormone synthesis and lends further support for a primary action of thyroid hormone at the nuclear level.

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“…Iopanoic acid and PTU inhibit hepatic 5'-monodeiodination (8,(20)(21)(22). Incubation of pituitary fragments with 13 ,uM iopanoic acid results in no alteration in the N:M ratio for T3(T3) but does result in a marked decrease in the N:M ratio for T3(T4) ( Table VIII) Incubation with 29 ,uM PTU had no demonstrable effect on the N:M for T3(T3) and did not reduce the N:M T3(T4) ratio. As a result, R was not lower, and in one case it was statistically higher than in controls from the same pool of pituitary fragments.…”

Section: Methodological Considerations Inmentioning

confidence: 99%

Physiological and Pharmacological Influences on Thyroxine to 3,5,3′-Triiodothyronine Conversion and Nuclear 3,5,3′-Triiodothyronine Binding in Rat Anterior Pituitary

Cheron¹,

Kaplan²,

Larsen³

1979

J. Clin. Invest.

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A B S T R A C T Our recent in vivo studies have suggested that intrapituitary L-thyroxine (T4) to 3,5,3'-triiodo-L-thyronine (T3) conversion with subsequent nuclear binding of T3 is an important pathway by which circulating T4 R. In fasted rats, neither N:M ratio was depressed, although hepatic T4 to T3 conversion in the same animals was 50% of control (P < 0.005). lopanoic acid (13 ,uM), but not 6-n-propylthiouracil (29 MM), decreased the N:M ['251]T3 with a significant decrease in the value for R (P < 0.025 or less). Neither sodium iodide (6 ,uM) nor thyrotropin-releasing hormone (7-700 nM) affected the T3 N:M ratios. These results indicate that intrapituitary T4 to T3 conversion is stimulated in hypothyroidism and depressed in T4-treated animals, whereas opposite changes occur in hepatic T4-5'-monodeiodination. Unlike liver, anterior pituitary T4-5'-monodeiodination is not affected by fasting or incubation with 6-n-propyl-2-thiouracil, but T4 to T3 conversion is inhibited in both by iopanoic acid. These results indicate that there are important differences between anterior pituitary and other tissues in the regulation of T4-5'-monodeiodination.

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Limited Binding Capacity Sites for l-Triiodothyronine in Rat Liver Nuclei

Cited by 167 publications

References 21 publications

Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal.

Glucose and triiodothyronine both induce malic enzyme in the rat hepatocyte culture: evidence that triiodothyronine multiplies a primary glucose-generated signal.

Thyroid hormone stimulates de novo growth hormone synthesis in cultured GH1 cells: evidence for the accumulation of a rate limiting RNA species in the induction process.

Physiological and Pharmacological Influences on Thyroxine to 3,5,3′-Triiodothyronine Conversion and Nuclear 3,5,3′-Triiodothyronine Binding in Rat Anterior Pituitary

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