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The chemical nature of the iodocompounds is discussed below ( pp. 76 et seq. ).

C.

Thyroglobulin synthesis

Little is known of the synthetic mechanisms for formation of thyroglobulin.

Its synthesis has not been demonstrated in cell-free systems, nor has its synthesis by systems with intact thyroid cells in vitro been unequivocally proven.

There is some reason to think that thyroglobulin synthesis may proceed independently of iodination, for in certain transplantable tumours of the rat thyroid containing essentially no iodinated thyroglobulin, a protein that appears to be thyroglobulin has been observed in ultracentrifuge experiments ( Wolff, Robbins and Rall, 1959 ).

Similar findings have been noted in a patient with congenital absence of the organification enzymes, whose thyroid tissue could only concentrate iodide.

In addition, depending on availability of dietary iodine, thyroglobulin may contain varying quantities of iodine.

D.

Secretion

Since the circulating thyroid hormones are the amino acids thyroxine and tri-iodothyronine ( cf. Section C ), it is clear that some mechanism must exist in the thyroid gland for their release from proteins before secretion.

The presence of several proteases and peptidases has been demonstrated in the thyroid.

One of the proteases has pH optimum of about 3.7 and another of about 5.7 ( McQuillan, Stanley and Trikojus, 1954 ; ;

Alpers, Robbins and Rall, 1955 ).

The finding that the concentration of one of these proteases is increased in thyroid glands from TSH-treated animals suggests that this protease may be active in vivo.

There is no conclusive evidence yet that either of the proteases has been prepared in highly purified form nor is their specificity known.

A study of their activity on thyroglobulin has shown that thyroxine is not preferentially released and that the degradation proceeds stepwise with the formation of macromolecular intermediates ( Alpers, Petermann and Rall, 1956 ).

Besides proteolytic enzymes the thyroid possesses de-iodinating enzymes.

A microsomal de-iodinase with a pH optimum of around 8, and requiring reduced triphosphopyridine nucleotide for activity, has been identified in the thyroid ( Stanbury, 1957 ).

This de-iodinating enzyme is effective against mono- and di-iodotyrosine, but does not de-iodinate thyroxine or tri-iodothyronine.

It is assumed that the iodine released from the iodotyrosines remains in the iodide pool of the thyroid, where it is oxidised and re-incorporated into thyroglobulin.

The thyroxine and tri-iodothyronine released by proteolysis and so escaping de-iodination presumably diffuse into the blood stream.

It has been shown that thyroglobulin binds thyroxine, but the binding does not appear to be particularly strong.

It has been suggested that the plasma thyroxine-binding proteins, which have an extremely high affinity for thyroxine, compete with thyroglobulin for thyroxine ( Ingbar and Freinkel, 1957 ).

E.