Thyroglobulin biosynthesis: An ultracentrifugal study

Thomson, John Alexander (1969) Thyroglobulin biosynthesis: An ultracentrifugal study. MD thesis, University of Glasgow.

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Abstract

This work presents data on the biosynthesis of thyroglobulin. This protein of 19S size constitutes the main thyroid protein in most normal vertebrate thyroid glands; smaller amounts of 3-8S and 27S protein are usually present. Initially it is shown that in vivo in the rat, as has been previously shown in vitro by other workers, labelled amino acids are incorporated into proteins of 3-8S and 12S size before the label is incorporated into thyroglobulin. The pattern of incorporation is consistent with the 12S and with less certainty the 3-8S proteins being precursor subunits of the 19S protein. At long time intervals after administration of a pulse of 3H-leucine, the pattern of labelling of the 3-8S fraction could also be consistent with this labelled fraction being a breakdown product of the labelled 19S protein. These findings with 3H-leucine are in contrast to those seen when [125]I is used. In this case [125]I is not incorporated into proteins <18S, except for a small percentage transiently incorporated into a 12S protein at very early time intervals after administration of the label. At no time, however, was a protein lighter than 18S present as the predominant labelled peak. The production of a goitrous state in the rat, by means of one of the antithyroid drugs which block at various points the biosynthesis of thyroxine, alters the distribution of the thyroid proteins. Thyroglobulin diminishes in amount whereas the 3-8S proteins increase; the normally present 27S peak is lost and a new OD peak is seen in the 32S region. In these goitrous glands the incorporation of 3H-leucine into the thyroid proteins is enhanced, but a truly 19S protein is not formed. As would be anticipated, 125 the incorporation of [125]I is blocked to a varying degree depending on the potency of the goitrogen used. When a mild iodine deficiency state is induced by feeding a low iodine diet, the incorporation of 3H-leucine or [125]I into thyroglobulin is accelerated, presumably due to increased TSH production by the pituitary. When a more severe degree of iodine deficiency is present, an 18S, as opposed to a truly 19S protein, is labelled. There is comparatively little labelling of the 3-8S proteins of iodine deficient glands, as compared to drug-induced goitres. The administration of T4 to a goitrous, or normal, animal virtually inhibits the incorporation of 3H-leucine and, to a lesser extent, [125]I into the thyroid proteins, A stable 12S protein peak is seen under these conditions, which suggests that this may represent a failure of incorporation of sub-units into 19S thyroglobulin. An [125]I labelled 12S protein of high specific activity is found during withdrawal of antithyroid drugs in the rat. The protein patterns of a series of 100 human thyroid glands were studied. The normal human thyroid gland showed a protein pattern similar to the rat and slices of the tissue incorporated 3H-leucine into the 19S protein and its presumed sub-units in vitro. [125]I on the other hand was incorporated only into an 18-19S protein. In thyrotoxicosis, whether prepared pre-operatively by carbimazole/iodide or by KC104, the notable feature was the loss of proteins > 19S. This occurred despite differences in distribution of the thyroid proteins in thyroid glands treated pre-operatively with these two different regimes. (Abstract shortened by ProQuest.).

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: E M McGirr
Keywords: Biochemistry
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72964
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06
URI: https://theses.gla.ac.uk/id/eprint/72964

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