THYROID HORMONE-DEPENDENT REPRESSION OF ALPHA-1-MICROGLOBULIN BIKUNINPRECURSOR (AMBP) GENE-EXPRESSION DURING AMPHIBIAN METAMORPHOSIS/

A Xenopus AMBP (xAMBP) cDNA clone was isolated from a subtracted liver cDNA library by differential hybridization screening. The deduced ami no acid sequence shared 50-60% identity with its mammalian counterpart s, which are the precursors of the plasma glycoproteins, alpha 1-micro globulin and bikunin. Both peptide structures were well conserved in x AMBP. Northern and in situ hybridization revealed that the xAMBP gene was specifically expressed in liver parenchymal cells. The gene was ac tivated around embryo hatching and repressed at the metamorphic climax stage. During adult life the mRNA level remained low. Treating the ta dpoles with thyroid homone prematurely reduced the mRNA level. Further more, thyroid hormone acted on larval hepatocytes in primary culture a nd reduced the mRNA level. Thus, xAMBP gene expression appears to be r epressed through the direct action of thyroid hormone on the hepatocyt es at the metamorphic climax stage. On the other hand, adult hepatocyt es in thyroid hormone-free culture medium expressed mRNA at a low leve l, which was not reduced in response to thyroid hormone, suggesting th at the repressed xAMBP gene expression in adult hepatocytes was mainta ined in a thyroid hormone-independent manner. The unique expression pr ofile suggested that the xAMBP gene plays a biological role in the pro gression of amphibian metamorphosis.