Some tissues do not seem to be responsive to thyroid hormones. For instance, thyroid hormones instruct the ventral retina to express ephrin B and to generate the ipsilateral neurons seen in Figure 21.1D. The dorsal retina, however, is not responsive to thyroid hormones and does not generate new neurons. The dorsal retina appears to be insulated from thyroid hormones by expressing deiodinase III, which degrades the T3 produced by deiodinase II. If deiodinase III is activated in the ventral retina, neurons will not proliferate and no ipsilateral axons will form (Kawahara et al. 1999; Marsh-Armstrong et al. 1999).
The frog brain also undergoes changes during metamorphosis, and one of its functions is to downregulate metamorphosis once metamorphic climax has been reached. Thyroid hormones eventually induce a negative feedback loop, shutting down the pituitary cells that instruct the thyroid to secrete them (Saxén et al. 1957; Kollros 1961; White and Nicoll 1981). Huang and colleagues (2001) have shown that, at the climax of metamorphosis, deiodinase II expression is seen in those cells of the anterior pituitary that secrete thyrotropin, the hormone that activates thyroid hormone expression. The resulting T3 is thought to activate genes that block secretion of thyrotropin, thereby initiating the negative feedback loop so that less thyroid hormone is made (Sternberg et al. 2011).