In vivo, cAMP stimulates growth and morphogenesis of mouse mammary ducts

In culture, cAMP is known to be mitogenic for mammary cells and several other epithelia, but evidence for a similar role in vivo has been only correlative. We have used plastic implants to cause slow release of cholera toxin and other cAMP-active agents to local areas of mammary glands in ovariectomized mice. Elevated levels of intracellular cAMP around the implants promoted vigorous growth and normal ductal morphogenesis, while distant sites were unaffected. Local effects of cAMP included restoration of normal ductal caliber, formation of new end buds, and reinitiation of DNA synthesis in both epithelium and surrounding stroma. Thus, cAMP is both a mitogenic and a morphogenetic factor in this tissue.