Requirements for T4-induced TSH suppression

3,3´,5´-triiodothyronine (T3) and thyroxine (T4) suppress thyroid-stimulating hormone (TSH) release from hypothyroid thyrotrophs. This effect is blocked by inhibitors of mRNA or protein synthesis, indicating that specific proteins are required. Marsili and colleagues have elucidated the requirements for this suppression. They found a greater than 50% reduction in TSH secretion in wild-type hypothyroid mice administered T3 or T4, but no increase in thyrotropin-releasing hormone (TRH) mRNA in the paraventricular nucleus, suggesting that a decrease in TRH synthesis is not required for the inhibition of TSH.

When using type 2 iodothyronine deiodinase knock-out (D2KO) mice, they found that the suppression of TSH was absent in mice administered with T4 as T4 requires D2 to convert T4 to T3. mRNA of pyroglutamyl peptidase II (PPII) (which inactivates TRH) was increased by T3, but not T4, in D2KO mice. This increase in PPII and the consequent inactivation of TRH could play a role in the suppression of TSH release by T3/T4. Thus, the rapid suppression of TSH by T3, does not occur due to a decrease in TRH mRNA, but TRH may be inactivated by rapid gene transcription of PPII in the tanycytes. Marsili et al. (2011) Journal of Endocrinology 211 73–78.

Read the full article at: DOI:10.1530/JOE-11-0248.