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Thyroid hormone deiiodinases

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Colquhoun, Eric Quentin (1982) Thyroid hormone deiiodinases. PhD thesis, University of Tasmania.

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Abstract

Assay systems involving iodine-125 labelled iodothyronine substrates
have been established which can detect deiodination with high sensitivity.
A HPLC separation has also been established which complements the radiochemical
assays.
Using these assays, 5'-deiodinase enzyme activities have been
localized to the plasma membranes, to the endoplasmic reticulum and to the
lysosomes prepared from liver and kidney homogenates. A further activity
in the cytosol of these tissues was also found, but evidence suggested,
in part, that its presence there may be due to an artefact of the
homogenisation procedures.
Purification studies were performed on the cytosol 5'-deiodinase
(because of its solubility) and on the combined microsomal 5'-deiodinase
activity. Substantial purification (300 fold) of the 5'-deiodinase from
cytosol was achieved using thyroxine as the ligand in affinity chromatography.
Gel electrophoresis of this purified product suggested the presence of only
a small number of proteins which combine in a regular fashion to produce
aggregates of related structures. The combined plasma membrane and endoplasmic reticulum microsomal
activity was significantly purified (3-10 fold) using iopanoic acid
(which is a 5'-deiodinase inhibitor) as the ligand in affinity
chromatography. The degree of purification compares favourably to that
achieved by other workers.
A model for deiodination of T4 is suggested in which the production
of both T3 and rT 3 occurs predominantly at the plasma membrane. The rT 3
produced is then subject to rapid catabolism by deiodination in the lysosome. The rate of rT 3 deiodination by lysosomes is controlled by the inhibition
or stimulation of lysosomal autophagy or changes in the lysosomal membrane
or both by drugs, hormones or aminoacids. This leads to alterations in
the intracellular levels of rT 3 which in turn feeds-back negatively on the
plasma membrane enzyme (and also perhaps the endoplasmic reticulum
deiodinase) to inhibit the production of T3. This then leads to a rise
in plasma rT 3 followed soon after by a fall in plasma 13.
It is further postulated that the final common pathway for dietary
changes of rT 3 /T 3 levels is via the intracellular levels of aminoacids
in the liver, especially those (e.g. Asn, Gln, Leu) which are gluconeogenic
or anabolic.
Finally drugs which are known to be lysomotrophic and markedly
affect the stability of lysosomes are predicted to have effects on the
ratio of rT3 to T3 found in plasma.

Item Type: Thesis (PhD)
Keywords: Thyroid hormones, Thyroxine, Iodine in the body
Copyright Holders: The Author
Copyright Information:

Copyright 1982 the Author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (Ph.D) - University of Tasmania, 1983. Bibliography: l. 214-244

Date Deposited: 25 Nov 2014 00:43
Last Modified: 19 Jul 2016 02:25
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