Regulation of rat cerebrocortical and adenohypophyseal type II 5'-deiodinase by thyroxine, triiodothyronine, and reverse triiodothyronine.
To further understand the regulation of type II iodothyronine 5'-deiodinase (5'D-II) in the central nervous system and pituitary, we examined the response of this enzyme to the acute administration of T4, T3, and rT3 in hypothyroid rats. Enzyme levels were correlated with serum concentrations of T4 and T3 in thyroidectomized rats after acute administration of either iodothyronine and in animals with hypothyroidism of increasing severity induced by methimazole administration. Estimates of the tissue concentrations of the three iodothyronines, nuclear T3, and serum TSH levels were used to assess mechanisms and intrinsic potencies of the three iodothyronines. In four experiments, doses of T4 that reduced 5'D-II activity by 50% (ID50) ranged from 0.18-0.39 micrograms/100 g BW in the cortex and from 0.34-1.05 in the pituitary, whereas the corresponding ID50 values of rT3 were 1.0 and 3.5, and those of T3 were 4.0 and 5.0 micrograms/100 g BW. T3 doses that saturated nuclear receptors and fully suppressed TSH showed only modest suppression of 5'D-II levels in the cortex and pituitary. Based on estimates of the tissue hormone levels resulting in 5'D-II suppression, T4 and rT3 were much more potent than T3 in decreasing 5'D-II. These findings support the concept that the effect of these iodothyronines on 5'D-II is not mediated by the nuclear T3 receptor. The correlation of serum T4 and T3 with enzyme levels after acute injections of T4 or after chronic treatment with methimazole suggested that plasma T4 is probably the main physiological signal regulating 5'D-II. It is conceivable that rT3 produced locally from T4 also plays a role in the regulation of the enzyme.
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D007037:Hypothyroidism / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism*; D008297:Male; D008713:Methimazole; D010544:Peroxidases / Q000378:metabolism*; D010902:Pituitary Gland / Q000201:enzymology; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy; D013972:Thyrotropin / Q000037:antagonists & inhibitors; D013974:Thyroxine / Q000494:pharmacology*; D013997:Time Factors; D014285:Triiodothyronine, Reverse / Q000494:pharmacology*
D008713:Methimazole; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D010544:Peroxidases; D007453:Iodide Peroxidase; D013974:Thyroxine