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

我们研究了β-和γ-酪蛋白mRNAs的聚(A)尾长对哺乳期小鼠乳腺mRNAs稳定性的影响。在实验一中，泌乳乳腺根据乳汁的积累和排出，对酪蛋白基因的聚(A)尾长进行了明显和可逆的调节。长的聚(A)不受核糖核酸酶(RNase)降解。因此，短聚(A)尾的酪蛋白信使核糖核酸的半衰期比长的短。检测了不同孕期和哺乳期酪蛋白基因的聚(A)尾长。在怀孕期间，Poly(A)尾巴大约有30个核苷酸长。酪蛋白基因一旦表达，聚(A)尾巴就会延长到100多个核苷酸。哺乳期结束时，随着多聚(A)尾巴的伸长，乳腺活动减弱，长度显著缩短。在哺乳期，长聚(A)尾巴的酪蛋白基因比短尾巴的酪蛋白基因更稳定。我们明确了乳腺通过改变酪蛋白mRNA的聚(A)尾长来调节酪蛋白mRNA的稳定性，酪蛋白mRNA的水平是在转录后水平上调节的。在实验二中，我们检测了TIM23mRNA在乳汁发生过程中的表达。TIM23是由基因组DNA编码的内膜蛋白转位酶线粒体。TIM23基因的表达受激素的调节，在妊娠末期表达增强。TIM23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.