In addition to the obvious morphological changes, important biochemical transformations occur during metamorphosis as T3 induces a new set of proteins in existing cells. One of the most dramatic biochemical changes occurs in the liver. Tadpoles, like most freshwater fish, are ammonotelic—that is, they excrete ammonia. However, like most terrestrial vertebrates, many adult frogs (such as the genus Rana, although not the more aquatic Xenopus) are ureotelic: they excrete urea, which requires less water than ammonia excretion. During metamorphosis, the liver begins to synthesize the enzymes necessary to create urea from carbon dioxide and ammonia (Figure 1).

T3 may regulate this change by inducing a set of transcription factors that specifically activates expression of the urea-cycle genes while suppressing the genes responsible for ammonia synthesis (Cohen 1970; Atkinson et al. 1996, 1998). Mukhi and colleagues (2010) showed that T3 activates adult hepatic genes while repressing larval hepatic genes in the same cell. Moreover, for a brief time during metamorphosis, the same liver cell contains mRNAs for both larval and adult proteins.  

Figure 1 Development of the urea cycle during anuran metamorphosis. (A) Major features of the urea cycle, by which nitrogenous wastes are detoxified and excreted with minimal water loss. (B) The emergence of urea-cycle enzyme activities correlates with metamorphic changes in the frog Rana catesbeiana. (After Cohen 1970.)

Literature Cited

Atkinson, B. G., A. S. Warkman and Y. Chen. 1998. Thyroid hormone induces a reprogramming of gene expression in the liver of premetamorphic Rana catesbeiana tadpoles. Wound Repair Regen. 6: 323–337.

PubMed Link

Atkinson, B. G., C. Helbing and Y. Chen. 1996. Reprogramming of genes expressed in amphibian liver during metamorphosis. In L. I. Gilbert, B. G. Atkinson and J. R. Tata (eds.), Metamorphosis: Postembryonic Reprogramming of Gene Expression in Amphibian and Insect Cells. Academic Press, San Diego, pp. 539–566.

Cohen, P. P. 1970. Biochemical differentiation during amphibian metamorphosis. Science 168: 533–543.

PubMed Link

Mukhi, S., L. Cai and D. D. Brown. 2010. Gene switching at Xenopus laevismetamorphosis. Dev. Biol. 338: 117–126.

PubMed Link

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