Dynamics and regulation of intracellular thyroid hormone concentrations in embryonic chicken liver, kidney, brain, and blood

Abstract

The intracellular thyroid hormone (TH) availability is influenced by different metabolic pathways. We investigated the relationship between tissue and plasma TH levels as well as the correlation with changes of deiodination and sulfation during chicken embryonic development. From day 14 until day 19, T 3 remains unchanged in liver and kidney in spite of increasing plasma T 4 and T 3 levels and a slightly increased T 4 availability in these tissues. During this period, the T 3 breakdown capacity by type III deiodinase (D3) is high in liver but low in kidney. The TH inactivation capacity of type I deiodinase (D1), with production of inactive rT 3 instead of T 3, in kidney seems to be potentiated by the sulfation pathway. A sharp rise in T 3 and T 4 is detected in all tissues examined when the embryo switches to lung respiration. The same day, T 4 content in liver is sharply enhanced and sulfation activity is decreased. So, T 4 availability in liver is increased while a declined D3 activity allows for the accumulation of hepatic T 3. The increase in renal T 3 and T 4 are more closely related to plasma TH profiles and a lack of correlation with the changes in renal D1 and D3 activity suggests that T 4 and T 3 content in this organ is strongly dependent on direct uptake from the blood. Despite much lower T 4 levels, T 3 levels in brain are in the same range as in liver and kidney and intracellular T 3 even exceeds the T 4 levels towards the end of development. The rise in TH content coincides with a drop in D3 activity, low sulfation activity and an increased T 3 production capacity via type II deiodinase (D2). In conclusion, the current study describes the dynamics of intracellular TH concentrations in liver, kidney, and brain during chicken development and investigates their relationship with circulating TH levels and changes of deiodinases and sulfotransferases. The clear differences in intracellular TH profiles among the different tissues demonstrate that circulating levels are not necessarily representative for the local TH changes. Some of the changes in intracellular TH availability can be linked to changes in local deiodination and sulfation capacities, but the importance of these enzyme systems in relation to other factors, such as hormone uptake, differs between liver, kidney, and brain.