Thyroid hormone metabolism and nuclear binding in Gunn rats

Abstract

We examined the serum concentrations of total, free thyroid hormones and TSH, activity of hepatic T4 5'-deiodinase, and T3 binding to hepatic nuclei in homozygous (j/j) and heterozygous (j/+) Gunn rats. Both total T3 and free T3 (FT3) concentrations in sera from j/j rats were significantly lower than those of j/+ rats on 5-10, 15-20, and 25-30 days after birth. Both total T4 and free T4 (FT4) concentrations in j/j and j/+ rat sera were not significantly different on 5-10 days. However, in j/j rats they were significantly higher than those of j/+ rats on days 15-20 and 25-30. Serum reverse T3 (rT3) concentrations were higher in j/j than in j/+ rats on days 5-10, 15-20, and 25-30. Serum TSH concentration in j/j and j/+ rats on 15 days post-natal were 1.42 +/- 1.28 and 1.65 +/- 1.24 micrograms/l (mean +/- SD), respectively, which were not significantly different from each other. T3 formation from T4 in hepatic microsomal fractions obtained 15 days after birth was significantly lower in homozygotes than in heterozygotes (4.89 +/- 1.18 vs 11.15 +/- 2.38 pmol/mg protein/min, p less than 0.005). Binding constants (Ka) as well as maximal binding capacities (MBC) for T3 of hepatic nuclei from 15 day-old j/j and j/+ rats were similar (ka; 3.58 x 10(9) vs 3.15 x 10(9) M-1, MBC; 0.316 vs 0.380 pmol/mg DNA). From these results we suggest that decreased conversion from T4 to T3 is one of the major reasons for high serum levels of T4 and rT3, and low levels of T3 in j/j rats, and that nuclear T3 binding and pituitary TSH secretion are unaltered in j/j rats.