Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1978 May; 61(5): 1247–1259.
PMCID: PMC372646
PMID: 207733

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

FURTHER EVIDENCE RELATING SATURATION OF PITUITARY NUCLEAR TRIIODOTHYRONINE RECEPTORS AND THE ACUTE INHIBITION OF THYROID-STIMULATING HORMONE RELEASE
J. E. Silva and P. R. Larsen
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Abstract

Injections 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 μg/dl T4 3 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 occupancy (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 T3 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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