EPIDERMAL GROWTH-FACTOR MODULATES CHOLERA-TOXIN INDUCED MAMMARY-GLANDDEVELOPMENT

Ovariectomized mice were either sham operated or sialoadenectomized an d injected daily for 18 days with saline, estradiol + progesterone, ch olera toxin or estradiol + progesterone + cholera toxin. Mammary devel opment score and DNA were increased by estradiol + progesterone, but n ot by cholera toxin alone. In combination with estradiol + progesteron e, cholera toxin increased mammary development score and mammary DNA. Sialoadenectomy reduced the ability of estradiol, progesterone and cho lera toxin to induce mammary development. In other experiments, mice w ere primed with estradiol + progesterone for 10 days, and mammary tiss ue removed for in vitro culture with various combinations of insulin, aldosterone, cholera toxin and epidermal growth factor. In combination with insulin and aldosterone, cholera toxin increased mammary develop ment in vitro. Sialoadenectomy reduced the ability of cholera toxin to induce mammary development in vitro. The effect of sialoadenectomy on mammary development was alleviated by adding epidermal growth factor to culture medium. Biochemical studies indicated that sialoadenectomy reduced the ability of estrogen and progesterone to induce cyclic AMP dependent protein kinase levels in mammary tissue, and also the abilit y of cholera toxin to induce accumulation of cyclic AMP in tissues. Th ese effects of sialoadenectomy were reversed by addition of EGF to cul ture media.