Sulfated tyrosines of thyroglobulin are involved in thyroid hormone synthesis

Thyroid hormone synthesis is under the control of thyrotropin (TSH), which also regulates the sulfation of tyrosines in thyroglobulin (Tg), We hypothe sized that sulfated tyrosine (Tyr[S]) might be involved in the hormonogenic process, since the consensus sequence required for tyrosine sulfation to o ccur was observed at the hormonogenic sites. Porcine thyrocytes, cultured w ith TSH but without iodide in the presence of [S-35]sulfate, secreted Tg wh ich was subjected to in vitro hormonosynthesis with increasing concentratio ns of iodide, A 63% consumption of Tyr[S] (1 residue) was observed at 40 at oms of iodine incorporated into Tg, corresponding to a 40% hormonosynthesis efficiency. In addition, hyposulfated Tg secreted by cells incubated with sodium chlorate was subjected to in vitro hormonosynthesis, With 0.5 Tyr[S] residue (31% of the initial content), the efficiency of the hormonosynthes is was 29%. In comparison, when hormonosynthesis was performed by cells, wi th only 0.25 Tyr[S] residue (16% of the initial content), the hormonosynthe sis efficiency fell to 18%, These results show that there exists a close co rrelation between the sulfated tyrosine content of Tg and the production of thyroid hormones. (C) 1999 Academic Press.