The Questions of Developmental Biology

To ensure that this timing system works, two of the organs most sensitive to thyroxine are
the thyroid itself and the pituitary gland, which regulates thyroid hormone production. Thyroid
hormones initially create positive feedback to the pituitary gland, causing the anterior pituitary to
induce the thyroid to produce more T 3 and T 4 (Saxén et al. 1957; White and Nicoll 1981). Later,
as an effect of metamorphosis, the thyroid partially degenerates, and inhibitors of thyroid
hormone functions are made (Goos 1978).
Molecular responses to thyroid hormones during metamorphosis
Thyroid hormones appear to work largely at the level of transcription, activating the
transcription of some genes and repressing the transcription of others (Lyman and White 1987;
Mathison and Miller 1987). The transcription of the genes for albumin, carbamoylphosphate
synthase, adult globin, adult skin keratin, and the Xenopus homologue of sonic hedgehog is
activated by thyroid hormones. The transcription of the sonic hedgehog gene in the intestine is
particularly interesting, since it suggests that the regional patterning of the organs formed during
metamorphosis might be generated by the reappearance of some of the same molecules that
structured the embryo (Stolow and Shi 1995; Stolow et al. 1997).
But these are relatively late responses to thyroid hormones. The earliest response to T 3 is
the transcriptional activation of the thyroid hormone receptor (TR) genes (Yaoita and Brown
1990; Kawahara et al. 1991). Thyroid hormone receptors are members of the steroid hormone
receptor superfamily of transcription factors. There are two major types of T 3 receptors, TR and
TRβ. Interestingly, the mRNAs and proteins of both TRs are present at relatively low levels in the
premetamorphosis tadpole and then increase before thyroid hormone is released or
metamorphosis begins (Table 18.2; Kawahara et al. 1991; Baker and Tata 1992). The thyroid
hormone receptors may bind to their specific sites on the chromatin even before thyroid hormones
are present, and they are thought to repress gene transcription. When T 3 or T 4 enters the cell and
binds to the chromatin-bound receptors, the hormone-receptor complex is converted from a
repressor to a strong transcriptional activator (Wolffe and Shi 1999). At this time, the synthesis of
TRs accelerates dramatically, coinciding with the onset of metamorphosis.
Table 18.2. Relative accumulation of TRa and TRb mRNA in Xenopus tadpoles following
treatment with T3 and prolactin
Relative units
Treatment TR TR β
None 505 24
T 3 1290 368
Prolactin + T 3 799