The effects of p-chlorophenoxyisobutyrate on the turnover rate and distribution of thyroid hormone in the rat

Abstract

A single dose of p-chlorophenoxyisobutyrate (CPIB) caused an apparent displacement of 131I-labeled thyroxine (T 4) from the plasma into the liver and it also increased the rate of T 4 disappearance from the plasma, liver, kidney, heart and skeletal muscle of the rat. Since T 4 disappeared at the same rate from all tissues, tissue T 4 must have been in equilibrium with plasma T 4. The effects of CPIB disappeared after 30–40 hr, and T 4 turnover rates regressed toward those seen in control animals. When CPIB was fed to animals for 2–3 wks, it caused the plasma PBI concentration to drop from 5·2 to 3·7 μg/100 ml. Although the absolute plasma “free T 4” concentration remained unchanged (2·5 mμg/100 ml), the relative amount of circulating hormone present as “free T 4” increased about 40 per cent when CPIB was given. The displaced T 4 was concentrated by the liver and to a lesser extent by the kidney, causing these organs to become “hyperthyroid” as evidenced by a large increase in the mitochondrial α-glycerolphosphate dehydrogenase activity. At the same time, the rest of the organism remained “euthyroid” as evidenced by a lack of change in metabolic rate and thyroid function.