Protein kinase activity in the rat mammary gland during pregnancy, lactation, and weaning: a correlation with growth but not with progesterone receptor levels.
A protein kinase activity fraction was defined in cytosols and membranes of mammary tissue isolated from rats during pregnancy lactation, and weaning. By partial purification on DEAE-cellulose columns, it was shown that this protein kinase activity is cAMP independent and that its preferential substrate is casein and not histone. This protein kinase activity is inhibited by the bioflavonoid quercetin at doses that do not inhibit cAMP-dependent protein kinase activity. The enzyme requires Mg2+ and is inactive in the presence of 10 mM Ca+2; these properties distinguish this activity from casein kinase activity found in the Golgi fraction and involved in milk protein processing. By following the physiological cycle of mammary gland development during pregnancy, lactation, and weaning, we found a close correlation between proliferation, expressed as the DNA content per gland, and quercetin-inhibited cytosolic protein kinase activity. Moreover, changes in this phosphorylating activity preceded the glandular growth changes. There was a less significant correlation between the growth process and protein kinase activity in the membrane fraction. The cytosolic cAMP-dependent protein kinase activity showed (only partial) correlation with growth only during pregnancy. Cytosolic progesterone receptor levels in mammary tissue were used as an estrogenic marker. Tissue growth correlated with progesterone receptor levels during pregnancy, where estrogens are the predominant hormones affecting tissue proliferation. However, no such correlation was found during lactation and weaning, when PRL is the major hormone affecting mammary gland growth. These results suggest that quercetin-inhibitable protein kinase activity is not merely another estrogenic marker, but represents more general regulatory activity which might be connected to growth processes of breast tissue.
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D007700:Kinetics; D007774:Lactation; D008321:Mammary Glands, Animal / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011374:Progesterone / Q000097:blood; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism*; D011986:Receptors, Somatotropin; D014886:Weaning
D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011986:Receptors, Somatotropin; D011374:Progesterone; D004958:Estradiol; D013006:Growth Hormone; D011794:Quercetin; D011494:Protein Kinases