An attempt to induce reversable hypothyroidism in sheep

Abstract

Two experiments were carried out as an attempt to develop a pharmacological method for suppression of thyroid gland function in Coopworth ewes.

Experiment 1 investigated the ability of triiodothyronine (T3) to suppress thyroid gland secretion in sheep. Ewes (n=6) were given a daily s.c. injection of T3 at doses of 0, 1,5 and 25 µg/kg live weight for 2 weeks. Treatment with T3 markedly lowered plasma T4 concentration in a logₑ dose-dependent manner (r= 0.96). Mean total plasma T3 concentration was increased and plasma TSH concentration was reduced in a dose-dependent manner by treatment with T3. Live weight was not significantly affected by treatment but sheep receiving the highest dose of T3 tended to have lowest weights. Heart rate was increased by logₑ (T3 dose) in a dose dependent manner (r = 0.85).

Experiment 2 investigated whether treatment with T3 and a goitrogen, MTU, administered separately or in combination, could suppress thyroid gland function in sheep. Thirty, 10-month-old Coopworth ewes were allocated randomly into 5 groups (n=6). Groups were: (A) Control, euthyroid, (B) THX, thyroidectomised, negative control, (C) MTU, daily oral drench with MTU at 35 mg/kg live weight for 9 weeks, (D) T3/MTU, daily s.c. injection of T3 at 5 µg/kg live weight for 5 weeks and then daily oral drench with MTU at 35 mg/kg live weight for 4 weeks and (E) T3+MTU, daily s.c. injection of T3 at 5 µg/kg live weight plus daily oral drench of MTU at 35 mg/kg live weight for 5 weeks, then daily MTU only for 4 weeks.

Mean total plasma T4 concentrations of T3 treated ewes groups (Groups D and E) were reduced to undetectable levels whilst the treatment was applied. On cessation of T3 administration plasma T4 concentrations rose within 1 week then declined over the final three weeks of MTU treatment. Sheep treated with MTU only (Group C) recorded a gradual, steady decline in mean plasma T4 concentration which reached undetectable levels at around 7 weeks of treatment. Mean plasma TSH concentration at week 7 in T3 treated ewes (Groups D and E) was marginally reduced by treatment. However in animals receiving MTU alone (Group C) plasma TSH concentration underwent a massive (9-fold) increase. Live weight was not significantly affected by treatment. T3 treatment increased (P<0.001) mean heart rate during weeks 7 to 9 (Groups D and E), whereas sheep receiving MTU only had a lower (P<0.05) mean heart rate than controls at week 12.

Thyroidectomised animals (Group B) had very low mean plasma T4 and T3 concentrations, very high plasma TSH concentration, no response to TRF challenge, highest mean live weight and the slowest mean heart rate throughout both studies. It is concluded that, (a) MTU treatment alone will suppress thyroid secretion in seven weeks, (b) T3 treatment, via negative feedback, causes profound and rapid suppression ofT4 secretion, and (c) pre treatment with T3, alone or in combination with MTU, is not more effective than MTU alone for thyroid gland suppression.