Effect of propylthiouracil-induced hypothyroidism on thyroid hormone profiles and tissue deiodinase activity in cashmere goats

The relationships between dose of propylthiouracil (PTU), circulating plasma thyroid hormone concentrations and 5'-monodeiodinase enzyme activity were investigated to determine the dose and duration of PTU treatment required to suppress plasma thyroid hormone levels in cashmere goats. Six groups of four cashmere goats were orally dosed for 2 months with between 1.1 and 35 mg/kg/bw per day of PTU. Mean thyroxine (T4) concentrations in goats treated with 1.1 mg/kg of PTU did not differ significantly from the control animals at any time during the study. However, in goats treated with 2.2 to 35 mg/kg/day of PTU, T4 concentrations declined in a dose dependent manner and plateaued after approximately 1 month of treatment. Mean plasma triiodothyronine (T3) concentrations were not significantly affected by any of the PTU doses. Type I 5'-monodeiodinase (type I 5'-MDI) activity in liver and kidney in the 1.1 mg/kg group was suppressed to 25 and 37%, respectively, of values recorded in control animals (24.3 vs. 98.4 for liver, and 15.7 vs. 42.4 pmol iodine released/h/mg protein for kidney), and was below assay sensitivity at doses of PTU > 4 mg/kg, Type II 5'-monodeiodinase activity in goat skin was detected at approximately 11.5 fmol iodine released/h/mg/protein and was not apparently affected by PTU treatment. It is concluded that a dose I 1 mg/kg/bw PTU can be used in long-term studies in goats, to inhibit extrathyroidal conversion of T4 to T3 via type I 5'-MDI without influencing circulating thyroid hormone profiles. (C) 1998 Elsevier Science B.V. All rights reserved.