Estrogen Control of Vitellogenin Gene Transcription and mRNA Stability

Abstract

We have analyzed the regulatory strategies used to achieve the massive, estrogen-mediated, induction of the mRNA coding for the egg yolk precursor protein, vitellogenin, in primary liver cultures of the amphibian Xenopus laevis. The induction of vitellogenin mRNA is achieved by three basic mechanisms: (a) an increase of at least several thousand fold in the absolute rate of vitellogenin gene transcription, which rises from undetectable levels to approximately 5 transcripts per gene per min., (b) an increase of approximately 20 fold in the absolute rate of total nuclear RNA synthesis, and (c) a selective stabilization of vitellogenin mRNA against cytoplasmic degradation. Vitellogenin mRNA is degraded with a half life of approximately 3 weeks in the presence of estrogen and exhibits a half life of 16 hours after estrogen is removed from the culture medium. The 30 fold increase in the stability of vitellogenin mRNA in the presence of estrogen is a specific, reversible cytoplasmic effect of the steroid hormone. Our measurements of the absolute rate of nuclear vitellogenin gene transcription and of the rate of appearance of the mRNA in the cytoplasm demonstrate that the average efficiency with which individual intervening sequences are excised from vitellogenin transcripts in vivo is at least 99%.