Suppression of thyrotropin by 3,5-dimethyl-3'-isopropyl-L-thyronine in euthyroid and hypothyroid rats.
The effect of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) a nonhalogenated thyroid hormone analog, on plasma and pituitary TSH levels was studied in euthyroid and 5-day-thyroidectomized (T-5d) rats. The minimal dose of DIMIT which suppressed basal plasma TSH for a 24-h period was 5.3 micrograms/100 g BW in the euthyroid rats and 5.2 micrograms/100 g BW in the T-5d group. The equipotent doses of T3 were 1.0 and 1.5 micrograms/100 g BW, respectively. Thus, the apparent DIMIT to T3 molar ratio ranged from 6.6 in the hypothyroid to 10 in the euthyroid group. The suppression of TRH-induced TSH release in the euthyroid rats required a high dose of DIMIT (9.2 micrograms/100 g BW), resulting in a DIMIT to T3 molar ratio of 17. Time-course studies comparing the effects of equipotent doses of DIMIT and T3 on TSH release rates in euthyroid and T-5d rats have shown a maximal suppression by 3--24 h after the administration of both T3 and DIMIT. However, the recovery from the effect was slower after T3. TSH synthesis in the T-5d group was similarly suppressed by DIMIT and T3. DIMIT has significant thyromimetic activity in euthyroid and hypothyroid rats, as evidenced by the suppresion of TSH synthesis and release.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D007037:Hypothyroidism / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013961:Thyroid Gland / Q000502:physiology*; D013970:Thyronines / Q000494:pharmacology*; D013972:Thyrotropin / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013970:Thyronines; D014284:Triiodothyronine; C022861:3,5-dimethyl-3'-isopropyl-L-thyronine; D013972:Thyrotropin; D013974:Thyroxine