Estrogen-induced destabilization of yolk precursor protein mRNAs in avian liver

In addition to regulating gene expression at the level of transcription, estrogen is generally considered to selectively stabilize induced mRNAs against degradation. As a result of mRNA stabilization, estrogen-induced mRNAs accumulate to much higher levels in target cells, and the encoded proteins are made at much greater rates than would occur on the basis of transcriptional activation alone. The present study examined the effect of estrogen on the stabilities of avian liver mRNAs that code for the yolk precursor proteins apolipoprotein (apo) II and vitellogenin (VTG) II. The results show that the degradation rates of apoII and VTG II mRNAs during hormone withdrawal are dramatically altered by the duration of prior estrogen treatment. During the 2 days required for the hormonal inductions of these mRNAs to new steady states, the turnover rates of both mRNAs were the same in the presence and absence of estrogen (t1/2 = 13 h). This result indicates that mRNA stabilization does not contribute to the extensive accumulation of apoII and VTG II mRNAs. When the duration of estrogen treatment was extended beyond 3 days, however, hormone withdrawal led to the rapid (t1/2 = 1.5 h) and selective destabilization of these mRNAs. This result suggests that estrogen induced a destabilization activity that was only functional following hormone withdrawal. Thus, the point at which estrogen alters mRNA stability is at the level of mRNA degradation. An absence of detectable apoII mRNA degradation intermediates during either the slow or rapid mode of mRNA decay suggests that the rate-limiting step for apoII mRNA turnover is an estrogen-sensitive targeting event that marks the mRNA for rapid degradation.