Inhibition of the response of thyrotrophin to thyrotrophin-releasing hormone by thyroxine in hypothyroid rats treated with iopanoic acid: evidence suggesting an intrinsic biological activity of thyroxine without prior conversion to 3,5,3'-tri-iodothyronine.

The effects of a physiological replacement dose of thyroxine (T4) on the response of plasma TSH to TRH in hypothyroid rats were studied. Animals were treated with iopanoic acid (IOP; 5 mg/100 g body weight) or vehicle 24, 12 and 1.5 h before the experiment. Thereafter, 800 ng T4/100 g body weight were administered i.v. and 20 min later 1 microgram TRH/100 g body weight was injected i.v. In control rats the basal concentration of TSH was 1450 +/- 300 (S.E.M.) mu./1. The plasma concentration of TSH 10 min after injection of TRH increased to 167 +/- 14% of the mean basal value (P less than 0.001). The injection of T4 significantly (P less than 0.005) reduced the TSH response to TRH in both IOP-treated (118 +/- 15%) and vehicle-treated (108 +/- 15%) rats compared with untreated controls. Tri-iodothyronine (T3) was undetectable in the plasma of all rats, whereas the plasma concentration of T4 was 121 +/- 19 nmol/l in IOP-treated and 139 +/- 23 nmol/l in vehicle-treated rats 30 min after injection of 800 ng T4/100 g body weight. In pituitary cells of control rats, cytoplasmic radioactivity 30 min after injection of [125I]T4 was 1.28 +/- 0.13 X 10(-2)% (76 +/- 6% T4 and 17 +/- 3% T3), whereas that in nuclei reached 0.42 +/- 0.36 X 10(-2)% (51 +/- 4% T4 and 28 +/- 3% T3) of the injected dose.(ABSTRACT TRUNCATED AT 250 WORDS)