A radioimmunoassay for murine thyroglobulin in serum: age-related increase of serum thyroglobulin levels in AKR/J mice.

Possible regulation of the synthesis of murine thyroglobulin (mTg) and a possible role for the major histocompatibility complex in this process were evaluated in 18 inbred strains of mice. A double antibody RIA was first developed to measure mTg in serum. The isolated mTG was labeled with 131I since 125I rapidly degraded the mTg molecule. The sensitivity of this mTg assay allowed detection of 15-20 ng/ml. Specificity was demonstrated by the minimal cross-reactivity with rat Tg (0.008%) and the total lack of cross-reactivity with human Tg. There was no correlation between H-2 haplotype and serum mTg levels. In five strains of mice with the H-2k haplotype, mTg levels varied from 30 +/- 2 to 48 +/- 11 ng/ml (mean +/- SD); however, only aged AKR/J mice (H-2k) exceeded this range (196 +/- 27 ng/ml). Strains with other haplotypes (a, b, d, g, q, v) demonstrated a similar range of mTg levels, but none had this age-related increase in mTg levels. The high levels of mTg were not caused by a decrease in the half-life of this protein and probably not caused by virus-induced alterations in the thyroid economy. Thyroids from the AKR/J mice, however, had larger follicles and flatter epithelia compared to thyroids from other strains. These studies suggest that AKR/J mice may represent a useful animal model for the study of goitrogenesis.