FIG. 1.

Central regulation of TH synthesis and TH metabolism. (A) Feedback system maintaining TH homeostasis. TRH secreted by the hypothalamus, stimulates the synthesis and secretion of TSH by the thyrotrophs, located in the anterior pituitary gland. TSH stimulates TH synthesis and secretion by the thyroid gland. TSH is also regulated by TH through a negative feedback system. (B) Activation and metabolism of TH. After active cellular uptake of TH through transmembrane transporters, the precursor 3,3′,5,5′-tetraiodothyronine (thyroxine, T4) is converted into the active 3,3′,5-triiodothyronine (T3) hormone or inactive 3,3′,5′-triiodothyronine metabolite (reverse T3, rT3). D1 and D2 are the principal enzymes that catalyze 5′-deiodination, converting T4 to T3 and rT3 to 3,′3-diiodothyronine (T2), while D3 catalyzes 5-deiodination, converting T4 to rT3 and T3 to T2.