H1 histone synthesis and phosphorylation in mouse mammary gland in vitro.

The synthesis and phosphorylation of H1 histones were studied in organ cultures of midpregnant mouse mammary glands exposed to various combinations of insulin, cortisol and prolactin over a 48-h period. The synthesis of specific H1 histone subtypes was changed only when all three hormones were present, and the effect was most pronounced during the first 24 h of culture, a period of cell replication. The 3-hormone combination also stimulated the phosphorylation of the N-terminal region of the H1 histone, and this also occurred maximally during the first 24 h of culture. The enhanced phosphorylation of the N-terminal region of the H1 histone included a site sensitive to phosphorylation by cyclic AMP-dependent protein kinase. Thus, hormones which stimulate mammary development in vitro influence the synthesis and specific phosphorylation of H1 histones during a period of cell replication preceding the expression of milk protein genes.