Comparison of inhibitory effects of 3,5,3'-triiodothyronine (T3), thyroxine (T4), 3,3,',5'-triiodothyronine (rT3), and 3,3'-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thyrotropin in the rat in vitro.

In order to compare, in vitro, the TSH suppressive effects of iodothyronines, rat pituitary quarters were first preincubated with T4, T3, rT3, or 3,3'-diiodothyronine (T2) in Gey and Gey buffer containing 1% bovine serum albumin for 2 h at 37 C and then incubated at 37 C for 1 h with the iodothyronine under study and TRH. TSH released into the medium during incubation was compared to that released by control pituitary fragments, which were not exposed to iodothyronines. All four iodothyronines (T3, T4, rT3, and T2) were able to significantly inhibit the TRH-induced release of TSH from pituitary fragments in a dose range of 0.015-2.2 microgram/ml. However, much larger doses of sodium iodide (1.25 mg/ml) and diiodotyrosine (10 and 30 microgram/ml) had no significant effect on the release of TSH. Among T3, rT3, and T4, T3 was the most potent and rT3 was the least potent. The relative potency of T3:T4:rT3 appeared to be approximately 100:12:1 when estimated from the lowest doses that caused significant inhibition of TRH-induced release of TSH, and approximately 100:6:0.5 when estimated from the doses that caused 50% inhibition of TSH release; the TSH inhibiting potency of T2 was similar to that of rT3. The activity of T4 could not be explained entirely on the basis of contamination of T4 with T3 or by in vitro conversion of T4 to T3. Similarly, the available data suggested that rT3 and T2 possess some, albeit modest, intrinsic TSH-Suppressive activity. TSH-inhibiting activities of T3, T4, and rT3 were also studied using pituitary fragments from starved and iodine-deficient rats. There was no evidence of a change in the sensitivity of the thyrotroph to either T3 or T4 in starvation. Similarly, comparison of the responses to several doses of rT3 did not indicate any significant abnormality in the sensitivity of the thyrotroph to rT3 in starvation or iodine deficiency. However, comparison of the TSH-suppressive effects of T4 in the iodine-deficient and normal rat indicated a significant increase in the sensitivity of the thyrotroph to T4 in iodine deficiency. A similar trend was also evident in the effect of T3 in iodine deficiency, but it fell short of statistical significance.