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 act ivity were investigated to determine the dose and duration of PTU trea tment required to suppress plasma thyroid hormone levels in cashmere g oats. 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 s ignificantly from the control animals at any time during the study. Ho wever, in goats treated with 2.2 to 35 mg/kg/day of PTU, T4 concentrat ions declined in a dose dependent manner and plateaued after approxima tely 1 month of treatment. Mean plasma triiodothyronine (T3) concentra tions 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 s ensitivity at doses of PTU > 4 mg/kg, Type II 5'-monodeiodinase activi ty in goat skin was detected at approximately 11.5 fmol iodine release d/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 studi es 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.