Timing of metamorphosis and the onset of the negative feedback loop between the thyroid gland and the pituitary is controlled by type II iodothyronine deiodinase in Xenopus laevis

Two important features of amphibian metamorphosis are the sequential respon se of tissues to different concentrations of thyroid hormone (TH) and the d evelopment of the negative feedback loop between the pituitary and the thyr oid gland that regulates TH synthesis by the thyroid gland. At the climax o f metamorphosis in Xenopus laevis (when the Tn level is highest), the ratio of the circulating precursor thyroxine (T-4) to the active form 3.5.3'-tri iodothyronine (T-3) in the blood is many times higher than it is in tissues . This difference is because of the conversion of T-4 to T3 in target cells of the tadpole catalyzed by the enzyme type II iodothyronine deiodinase (D 2) and the local effect (cell autonomy) of this activity, Limb buds and tai ls express D2 early and late in metamorphosis, respectively, correlating wi th the time that these organs undergo TH-induced change. T-3 is required to complete metamorphosis because the peak concentration of T-4 that is reach ed at metamorphic climax cannot induce the final morphological changes. At the climax of metamorphosis, D2 expression is activated specifically in the anterior pituitary cells that express the genes for thyroid-stimulating ho rmone but not in the cells that express proopiomelanocortin, Physiological concentrations of T-3 but not T-4 can suppress thyrotropin subunit P gene e xpression. The timing and the remarkable specificity of D2 expression in th e thyrotrophs of the anterior pituitary coupled with the requirement for lo cally synthesized T-3 strongly support a role for D2 in the onset of the ne gative feedback loop at the climax of metamorphosis.