Effects of active immunization against L-triiodothyronine on serum thyrotropin levels and liver mitochondrial α-glycerophosphate dehydrogenase activity in rats: evidence for reduced hormone disposal to cells

Abstract

Thyroid hormone binding autoantibodies have been observed in serum from patients affected by either thyroid disorders or autoimmune nonthyroid diseases.ln most instances, no major involvement of thyroid status of these patients has been reported. However, some authors have attributed the occurrence of hypothyroidism to high capacity thyroid hormone binding autoantibodies.In order to verify such a hypothesis, the effect of these autoantibodies on serum TSH and liver mitochondrial alpha-glycerophosphate dehydrogenase has been investigated in rats, wherein circulating T3-binding antibodies (max cap10⁻¹² 10⁻⁸ to mol/l) were induced by active immunization.Starting from the 3rd week after antigen injection, the binding of ¹²⁵I-T3 to serum immunoglobulins was progressively increased, with a peak at the 5th week. In immunized animals considered as a whole group, serum TSH levels were significantly higher and liver mitochondrial alpha-glycerophosphate dehydrogenase activity was significantly lower than in normal rats (m ± SE: 145 ± 15 vs 34 ± 2 ng/dl and 0.0450 ± 008 vs 0.0980 ± 005 ΔA. mg/prot/.min, respectively; p < 0.001) The pattern of both TSH increase and alpha-glycerophosphate dehydrogenase decrease were similar to the evolution of ¹²⁵-I-T3 binding to serum immunoglobulins, the maximal TSH values and lowest enzyme levels being observed at the 5th week after the beginning of the experiment. These results indicate that high capacity thyroid hormone binding autoantibodies may actually reduce thyroid hormone disposal at cellular level, at least prior to the attainment of steady state T3- antibody hormone binding.