Thyroid hormone induces a reprogramming of gene expression in the liver of premetamorphic Rana catesbeiana tadpoles

Abstract

During spontaneous or thyroid hormone-induced metamorphosis of the Rana catesbeiana tadpole, postembryonic changes occur in its liver that are permanent and necessary for the transition of this organism from an aquatic, ammonotelic larva to a semiterrestrial, ureotelic adult. These changes include the coordinated expression of genes encoding the urea cycle enzymes carbamyl phosphate synthetase and ornithine transcarbamylase. Although these changes are dependent on thyroid hormone and occur within the resident hepatocytes, the mechanism(s) by which this hormone reprograms gene expression in these cells and initiates the tissue-specific expression of these genes is poorly understood. Our contention is that the thyroid hormone-induced expression of these genes is an indirect effect of thyroid hormone and involves an early, thyroid hormone-induced upregulation of a gene(s) encoding a tissue-specific transcription factor(s), which in turn, upregulates in a coordinated fashion, the expression of these urea cycle enzyme genes. Herein, we present results that demonstrate a role for a Rana homologue of a mammalian transcription factor, C/EBPalpha(designated as RcC/EBP-1), in the thyroid hormone-induced cascade of gene activity responsible for reprogramming gene expression and initiating the coordinated expression of genes, such as carbamyl phosphate synthetase-I and ornithine transcarbamylase, which are characteristic of the adult liver phenotype.