Influence of Cholera Toxin (an Adenylate Cyclase Activator) on Deoxyribonucleic Acid Synthesis of Bovine Mammary Tissue In Vitro and in Athymic Nude Mice

Abstract

Bovine mammary tissue from midpregnant heifers was placed in explant culture to which chlorea toxin (a potent adenylate cyclase activator) was added (0 to 100ng/ml). Chlorea toxin increased incorporation of thymidine into DNA in the cultures; response was maximum with 10ng/ml chloera toxin and approximately 24h after addition of cholera toxin. In other studies, bovine mammary tissue was transplanted subcutaneously to ovariectomized athymic nude mice. Subsequent treatment of the mice with cholera toxin alone did not affect growth of bovine mammary tissue. However, treatment with estradiol plus progesterone increased DNA synthesis in epithelial cells. In estradiol plus progesterone-treated mice, cholera toxin injections further increased DNA synthesis. In addition, estradiol plus progesterone treatment in vivo (in athymic nude mice) increased DNA synthesis of bovine mammary tissue in response to cholera toxin in vitro. This synergism between cholera toxin and ovarian steriods may have been mediated, at least in part, by estradiol plus progesterone induction of cyclic AMP dependent protein kinase, as the activity of this enzyme was increased by estradiol plus progesterone.