Thyrotropin Regulates the Levels of Free Ubiquitin and Ubiquitin-Protein Conjugates in the Male Mouse Thyroid

The conjugation of ubiquitin to proteins can be a signal for their degradation, but can also be involved in regulatory processes not directly involved in protein degradation. Because thyrotropin (TSH) is the major physiological regulator of the thyroid, we have investigated whether changes in the circulating level of TSH influence the level of immunoreactive ubiquitin in the thyroid, as assessed by dot-blot assays. Putting male Balb/c mice on a low iodine diet with methimazole (MMI) in their drinking water for 14 days raised the level of ubiquitin by 425% (p < 0.001) per microgram nonthyroglobulin protein (the mean thyroglobulin level dropped by 35% (p < 0.05)). Western blots similarly indicated that immunoreactivity migrating in the region of monoubiquitin, ubiquitin oligomers, and ubiquitinated thyroid proteins increased on the low iodine/MMI diet. Injecting 1 μg triiodothyronine (T3) 6 hours prior to sacrifice appeared to reduce the ubiquitin levels by 31% when compared with mice only on the low iodine...