Expression in Xenopus oocytes revealed differential modes of regulation of the constitutive trans-activation domains present in the thyroid hormone receptor (TR) and its oncogenic homolog v-ErbA. The nuclear environment of oocytes induced a constitutive trans-activation function in TR, but not v-ErbA, at hormone-inducible thyroid hormone response elements (TREs), which was further enhanced by thyroid hormone at a subset of TREs. In contrast, DNA-protein interactions at a response element which is induced by unliganded TR in mammalian cells mediated constitutive trans-activation by both TR and v-ErbA. These findings indicate that the responses of the ligand-independent trans-activation domains of TR and v-ErbA to cell-specific and TRE-mediated induction are not equivalent. Pre-injection of nuclear protein extract from anterior pituitary cells converted v-ErbA into a strong constitutive activator at a response element from the rat growth hormone gene. Thus, the dominant negative phenotype of v-ErbA can be abolished by direct or indirect interactions with tissue-specific proteins. The growth-promoting properties of the v-erbA oncogene have so far exclusively been linked to dominant repression of the anti-mitogenic roles of TR and retinoic acid receptor. Ultrastructural analysis revealed that, when expressed in Xenopus oocytes, v-ErbA induced early to intermediate meiotic changes occurring prior to chromosome condensation. The effects of v-ErbA on cell cycle reentry in oocytes were not mimicked by a dominant negative mutant of TR, suggesting that v-ErbA did not initiate meiosis by antagonizing endogenous TR. v-ErbA-induced meiosis occurred independently of the cAMP/MPF signal pathway, but required mRNA synthesis and translation. These findings suggest that v-ErbA mediated the release from G2 arrest by activating expression of a cell cycle inducer(s).