Hormone-dependent beta-casein mRNA stabilization requires ongoing protein synthesis

Mol Endocrinol. 1989 Dec;3(12):1961-8. doi: 10.1210/mend-3-12-1961.


The role of ongoing protein synthesis in mediating the posttranscriptional effects of hormones on casein gene expression in the COMMA D mouse mammary epithelial cell line was investigated using the protein synthesis inhibitors, cycloheximide and anisomycin. When COMMA D cells were pretreated with insulin and PRL for 24 h, the addition of glucocorticoids induced a greater than 20-fold increase in beta-casein mRNA accumulation with an apparent lag of greater than 8 h. Addition of cycloheximide and anisomycin not only prevented this increase, but unexpectedly, resulted in the rapid disappearance of preexisting beta-casein mRNA with a half-life of approximately 2 h. Under the same conditions, the levels of beta-actin and histone H4 mRNAs were increased markedly. In contrast, when cells were pretreated with all three lactogenic hormones for 48 h before the addition of either protein synthesis inhibitors or actinomycin D, the effects of these inhibitors on the levels of beta-casein mRNA were greatly diminished. This differential sensitivity of beta-casein mRNA to protein synthesis inhibitors was observed only in cells pretreated for greater than 24 h with all three hormones. Experiments performed in the absence of inhibitors indicated that beta-casein mRNA has a long half-life even after hormone withdrawal. These results suggest that hormone-dependent stabilization of cytoplasmic beta-casein mRNA requires ongoing protein synthesis. Cells cultured in the presence of all three lactogenic hormones slowly accumulate a labile protein(s), which exerts a selective effect on casein mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / genetics
  • Animals
  • Anisomycin / pharmacology
  • Caseins / genetics*
  • Cell Line
  • Cycloheximide / pharmacology
  • Glucocorticoids / pharmacology*
  • Histones / genetics
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Prolactin / pharmacology*
  • Protein Processing, Post-Translational*
  • RNA, Messenger / metabolism*


  • Actins
  • Caseins
  • Glucocorticoids
  • Histones
  • RNA, Messenger
  • Anisomycin
  • Prolactin
  • Cycloheximide