ANDROGEN INHIBITION OF MAMMARY GLAND DIFFERENTIATION IN VITRO

Various androgens inhibit the rate of synthesis of DNA and casein by midpregnancy mouse mammary explants cultured on chemically defined medium. At the concentrations studied, androgens do not inhibit the "base line" rate of casein synthesis, but do prevent the augmentation in rate of casein synthesis occurring in vitro in the presence of insulin, hydrocortisone and prolactin. The reduced rate of casein synthesis in the presence of androgens represents an inhibition of mammary differentiation, and correlates well with the arrested histological development observed. DNA synthesis by mammary epithelial cells is stimulated by insulin; androgens inhibit DNA synthesis independently of the presence of other hormones by reducing the number of epithelial cells incorporating tritiated thymidine into DNA. Since grain counts above labeled cells are not reduced, androgens prevent the initiation of DNA formation. In the presence of varying concentrations of androgens the rate of hormone-dependent casein synthesis is directly proportional to the rate of DNA synthesis occurring in the preceding period. The results indicate that DNA synthesis and/or subsequent events in the cell cycle are prerequisites for hormone-dependent mammary differentiation.