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

Abstract

ABSTRACT 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 μg TRH/100 g body weight was injected i.v. In control rats the basal concentration of TSH was 1450 ± 300 (s.e.m.) mu./l. The plasma concentration of TSH 10 min after injection of TRH increased to 167 ± 14% of the mean basal value (P < 0·001). The injection of T4 significantly (P < 0·05) 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 × 10−2% (76 ± 6% T4 and 17 ± 3% T3), whereas that in nuclei reached 0·42 ± 0·36 × 10−2% (51 ± 4% T4 and 28 ± 3% T3) of the injected dose. In IOP-treated rats there was an increase in total cytoplasmic radioactivity (P < 0·05), with a decreased proportion of [125I]T3 (0·12 ± 0·07%; P < 0·01), whereas nuclear T3 was significantly (P < 0·005) lower than in controls (0·057 ± 0·025 vs 0·22 ± 0·022 pmol T3/mg DNA). Administration of 25 μg unlabelled T4 along with the tracer reduced cytoplasmic radioactivity in both control and IOP-treated rats (P < 0·05), without a detectable change in nuclear radioactivity. The results suggest that T4, at a physiological replacement dose, possesses an intrinsic capacity to regulate secretion of TSH following administration of TRH to hypothyroid rats. J. Endocr. (1987) 113, 349–354