Characterizations and Properties of Thyroid Iodoproteins from Severely Iodine-Deficient Rats

The iodoproteins from goitrous rat thyroid glands (300–800 mg), obtained by prolonged (20 months) and severe iodine deficiency, were isolated and characterized. The animals were given a low iodine diet (2 μg 1/100 g diet) containing 125I for 81 days (approach to equilibrium) and then they were pulse—labeled with 131I and 3H—leucine 2 hr prior to sacrifice. Thyroglobulinlike iodoproteins represented only 5% of the total protein in the crude soluble extract with 19 S comprising 90% and 27 S 10%. There was almost no iodine in 19 S while 27 S contained 0.12% iodine. Therefore a large proportion of the iodine stored in the soluble iodoproteins was due to the iodine in the 27 S protein. The turnover of iodine in 27 S, however, was much slower than in 19 S. In these severely iodine deficient animals the distribution of soluble thyroid iodoproteins was not significantly different from that observed in normal glands; the low iodine content, however, affects the stability of thyroglobulin. The iodinefree 19 S was more easily unfolded and dissociated into half—sized subunits than normal thyroglobulin. The proportion of covalently bound, undissociable 19 S molecules was also significantly smaller in the iodine—free thyroglobulin. Normally iodinated 19 S has only one or two sulfhydryl groups which react with 14C—iodoacetamide, whereas iodine—free thyroglobulin contains as many as 5 reactive sulfhydryl groups in water. This difference in free sulfhydryl groups indicates that iodine oxidizes sulfhydryl groups prior to and concomitant with its incorporation into tyrosyl residues and probably accounts for the increased stability of iodinated compared to uniodinated thyroglobulin. (Endocrinology92: 1241, 1973)