The Influence of Circulating Thyroxine Serum Concentration on Hepatic Thyroxine Deiodinating Activity in Rats

Summary

The influence of varying thyroid metabolic states, induced by thyroxine (T₄) application, upon type I T₄ deiodinating activity has been assessed in the rat liver. A series of 18 rats was thyroidectomized and treated with T₄ at various doses, ranging from 0 to 50 μg/kg b.w. Microsomal T₄ to triiodothyronine (T₃) deiodinating activity (5′DA) andT₄to reverse T₃ (rT₃) deiodinating activity (5DA) as well as cytosolic non protein bound thiol content (NP-SH) were determined in the liver; concentrations of T₄, T₃, and rT₃ were measured in the serum.

In the experimental rats, T₄ serum concentrations ranged from 1.3 μg/dI to 15.6 μg/dl (controls, 5 ± 0.2 μg/dl, mean ± SEM), T₃ varied between 33 μg/dl and 150 μg/dl (91 ± 3 ng/dl), and rT₃ between 2 μg/dl and 25 μg/dl (7 ± 2 ng/dl). Relating T₄ to T₃ serum levels, a curvilinear relationship (power function, r = 0.94, p < 0.001), as described previously in man, was confirmed in the rats, as was the linear relationship between T₄ and rT₃ serum levels (r = 0.75, p < 0.001).

Individual 5′DA increased by more than fourfold, from 531 μg/mg. min to 2,234 pg/mg. min (controls, 1,419 ± 67 pg/mg min), when passing from low to high T₄ serum values. The increase in 5′DA was steeper in the low T₄ range, while it was progressively flattened under T₄ levels above the controls' range. The particular changes in 5′DA can be illustrated by calculating the ratio of 5′DA and T₄ serum levels. A greater than two fold drop in 5′DA/T₄ ratio, from about 700 to 250, occurred, as T₄ serum concentration increased from very low values to 5 μg/dl. Above 5 μ/dl, the 5′DA/T₄ ratio gradually declined to about 100, as T₄ serum concentrations were rising up to 15.6 μ/dl. No systematic association could be revealed between T₄ serum concentrations and 5DA (r = 0.08, p > 0.5). Cytosolic NP-Sil content was virtually identical among the control and the experimental group. A close and linear associated was obtained, when the T₃ to T₄ serum concentration ratio was related to the 5′DA/T₄ ratio (5 = 0.88, p < 0.001).

This study demonstrates, that circulating T₄ serum concentrations exert their stimulating influence upon hepatic 5′DA to a divergent extent in the low as compared to the elevated T₄ serum concentration range. The data provide direct evidence for T₄ induced alterations in peripheral type I 5′DA efficiency; the latter may be reflected by the T₃/T₄ serum concentration ratio in athyreotic individuals. Our results support the concept of an extrathyroidal system which operates besides and complementary to the pituitary-thyroid axis for sustaining T₃ serum concentrations.

Key words

Thyroxine - Hepatic thyroxine deiodinating activity - Rat