THE RELATIONSHIP BETWEEN MAMMARY GROWTH AND LACTATIONAL ACTIVITY AT THE MOLECULAR LEVEL

我们研究了β-和γ-酪蛋白mRNA的poly（A）尾长度对泌乳小鼠乳腺中mRNA稳定性的影响。在实验Ⅰ中，泌乳期乳腺对酪蛋白mRNA的poly（A）尾长度进行了可逆的调节，其调节依赖于乳腺乳汁的积累和排出。长poly（A）保护mRNA不被RNA酶降解。因此，具有短poly（A）尾的酪蛋白mRNA的半衰期比具有长poly（A）尾的酪蛋白mRNA的半衰期短。在妊娠和哺乳的不同阶段检测酪蛋白mRNA的poly（A）尾长度。在妊娠期间，poly（A）尾的长度约为30个核苷酸。一旦酪蛋白mRNA表达，聚（A）尾延长至超过100个核苷酸。泌乳末期乳腺对poly（A）尾伸长的反应较泌乳早期和中期减弱，poly（A）尾长度显著缩短。在泌乳期，长poly（A）尾的酪蛋白mRNA比短poly（A）尾的酪蛋白mRNA更稳定。研究表明，乳腺通过改变酪蛋白mRNA的poly（A）尾长度来调节酪蛋白mRNA的稳定性，酪蛋白mRNA的水平在转录后水平上受到调控。在实验II中，我们研究了在泌乳时Tim 23 mRNA的表达。Tim 23是一种线粒体内膜蛋白转位酶，由基因组DNA编码。Tim 23 mRNA的表达受激素的调节，在妊娠末期表达增加。Tim 23基因表达所需的激素基本上与牛奶合成所需的激素相同。

We examined the effect of the poly(A) tail length of β- and γ- casein mRNAs on the mRNA stability in the lactating mouse mammary gland. In the experiment I, the lactating mammary gland modulated acutely and reversibly the poly(A) tail length of casein mRNA depending on the accumulation and removal of gland's milk. The long poly(A) protected from mRNA degradation by RNases. Thus, casein mRNA with the short poly(A) tail had a shorter half-life than that with the long one. The poly(A) tail length of casein mRNA was examined a different stages of pregnancy and lactation. The poly(A) tail was about 30 nucleotides in length during pregnancy. Once casein mRNA was expressed, the poly(A) tail elongated to over 100 nucleotides. At the end of lactation, the mammary gland became less active in the elongation of the poly(A) tail than that at early and midlactation, and the poly(A) tail in length was shortened significantly. Casein mRNA with the long poly(A) tail was more stable than that with the shot one during lactation. We cleared that the mammary gland modulated the casein mRNA stability by changing the poly(A) tail length of casein mRNA, and that the level of casein mRNA was regulated at the posttranscriptional level. In the experiment II, we examined the expression of Tim23 mRNA at lactogenesis. Tim23, a mitochondrial of translocase of inner membrane protein, is encoded by genomic DNA. The expression of Tim23 mRNA was regulated by hormones and increased at the end of pregnancy. Hormones required for the Tim23 gene expression were essentially the same as for milk synthesis.