Contributions of Plasma Triiodothyronine and Local Thyroxine Monodeiodination to Triiodothyronine to Nuclear Triiodothyronine Receptor Saturation in Pituitary, Liver, and Kidney of Hypothyroid Rats: <i>FURTHER EVIDENCE RELATING SATURATION OF PITUITARY NUCLEAR TRIIODOTHYRONINE RECEPTORS AND THE ACUTE INHIBITION OF THYROID-STIMULATING HORMONE RELEASE</i>

J. E. Silva; P. R. Larsen

doi:10.1172/JCI109041

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

Published May 1, 1978 - More info

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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.

J. E. Silva and P. R. Larsen

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J. E. Silva and P. R. Larsen

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