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Title: The expression, regulation and selenium dependence of thyroidal 5'-iodothyronine deiodinase
Author: Beech, Stuart Geoffrey
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1994
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Thyroidal ID-I activity varied greatly between species, with the highest activities being found in the omnivores (rat, man, guinea-pig and mouse), while in herbivores (cattle, sheep, goat, rabbit, pig, llama and deer) thyroidal ID-I was < 0.3% of the activity found in the rat. The livers of all species studied showed similar, and relatively high levels of hepatic ID-I activity. Primary cultures of sheep and human thyrocytes were established and were shown to produce T3 in a dose-dependent fashion with respect to thyrotrophin (TSH). Using various inhibitors of ID-I activity and de novo synthesis sheep thyrocytes were found to produce T3 by de novo synthesis only. In contrast, human thyrocytes produced T3 solely by deiodination of endogenous thyroxine (T4), catalysed by ID-I. In addition, T3 production was demonstrated to be dependent on iodine supply in sheep but not human thyrocytes. Incorporation of 125I into T3 and T4 was only observed with TSH stimulated sheep thyrocytes. Using human thyrocytes in primary culture I have confirmed that stimulation of ID-I expression by TSH occurred via the cyclic-AMP second messenger pathway. These studies show that: a) thyroidal ID-I expression varies greatly between species, b) human thyrocytes in primary culture utilize ID-I for T3 production, while sheep thyrocytes rely on de novo synthesis, c) thyroidal ID-I expression is under the control of both the cAMP (+) and PI (-) second messenger pathways, and that d) thyroidal ID-I is a selenoprotein, protected from selenium deficiency possibly by an energy-dependent selenium uptake/trapping mechanism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available