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Intact rat thyroid lobes incubated in vitro release recently synthesized thyroglobulin (Tg) into the media at a faster rate than they release thyroglobulin stored in follicular structures. Differential release of this Tg fraction cannot be explained by morphological alterations in thyroid architecture during incubation. This rapidly excreted fraction exhibits a low density on rubidium chloride gradients characteristic of poorly sialylated and poorly iodinated thyroglobulin, comigrating on rubidium chloride gradients with thyroglobulin isolated from tunicamycin treated glands. This poorly sialylated and poorly iodinated thyroglobulin is itself unaffected in its density or release into the media by tunicamycin treatment. Tg isolated from the media of tunicamycin treated glands has nearly the same low iodine and low sialic acid content as rat serum thyroglobulin and does not incorporate radiolabelled glucosamine. This fraction thus appear to duplicate properties of low glycosylated-low iodinated thyroglobulin released from thyroid cells in organisms that have no follicular structures and no follicular storage process as well as from thyroid tissue in patients with thyroid disease states, particularly thyroid tumors. Thus it is proposed a "short loop" pathway of low-glycosylated low-iodinated thyroglobulin directly into circulation, that bypasses and is not stored in the follicular lumen, the "long loop".

Carbohydrate chains formation into thyroglobulin (Tg) is a prerequisite for thyroid hormones formation and completeness of carbohydrates chains is necessary for secretion of Tg into the follicles. Tg biosynthesis has been investigated by in vitro experiments, incubating rat thyroid glands with labeled amino-acid and carbohydrate in the presence of tunicamycin, a specific inhibitor of protein glycosylation. Tunicamycin inhibit Tg biosynthesis which is impaired in carbohydrate chains addition but slightly in the polypeptide synthesis, as shown by inhibition of 3H-glucosamine incorporation. Thus tunicamycin inhibits carbohydrate incorporation into Tg without affecting the polypeptide chain growth and decreases its secretion into the follicles.

Groups of rats have been treated for one month with a daily dose of 50 mg/kg of body weight/day of isoniazide a product used therapeutically in man against tuberculosis. The animals submitted to this experiment showed an increase of thyroid weight (39%) and a decrease of its content in water soluble proteins, including thyroglobulin and precursors. These proteins have been labeled in vitro by [3H]-4,5-L-leucine and by [3H]-galactose, by incubation of isolated glands during 4 h in a medium containing this labeled marker. The decrease of thyroglobulin-like proteins was of 20-37% for [3H]-D-1-galactose, labeled fraction and of 46-53% for the [3H]-leucine labeled fraction. Two thirds of the radioactive protein sedimented by ultracentrifugation in a sucrose gradient were present in a 12S monomer of thyroglobulin. This suggests an impairment of biosynthesis of 19S thyroglobulin, in which two of the subunit are associated. Under experimental conditions adopted this 19S protein was labeled by [3H]-leucine, but not by [3H]-galactose. Two other antituberculous agents studied, ethambutol and rifamizine, exerted not the same effects on thyroid gland in rats. Therefore a control of thyroid function appear to be necessarily only in man treated by isoniazine.

Thirty per cent of the iodine in thyroglobulin is present as iodothyronines. L-thyroxine (T4) represents 90-95% of hormonal iodine, 3,5,3'-triodo-L-thyronine (T3) contains at the most two per cent of it, 3,3'5'-triodo-L-thyronine (rT3) even less, as well as traces of 3,3'-diodo-L-thyronine. The plasma concentration of T4 is about 8 microgram per 100 ml, in the case of T3 it is 120 ng and 25 ng for rT3. The cell nucleus preferentially binds T3 and rT3 and there are also some specific mitochondrial proteins which possess a high affinity for T3. L-thyroxine is dehalogenated peripherically to T3, to take care of most of the requirements in T3. The enrichment of the plasma in rT3 has been shown to occur under various experimental and pathological conditoins. The blood level of T3 varies in inverse ratio to the level of rT3 and it shows that the peripheral formation of one is compensated for by the other. The excess of the prehormone T4 is metabolised as 3,5,3',5'-tetraiodothyroacetic acid (TetrAc); its level in the blood varies in the same way as the level of T3, in particular it decreases during starvation.