Specificity of tissue interaction and origin of mesenchymal cells in the androgen response of the embryonic mammary gland.

In the androgen-induced destruction of the mammary rudiments of 14 day male mouse fetuses, the hormone acts directly only on the mesenchyme, which then condenses around the epithelial gland buds and--in some unknown way--causes their necrosis. In this paper we report that an organ-specific but not species-specific influence of mammary epithelium on the surrounding mesenchyme is required to allow its response to the hormone. This epithelial "signal" has a very short range; its transmission may depend on contact between the two tissues. The requirement for epithelial contact, however, may only exist for those mesenchymal cells that initiate the reaction at the tissue interface, whereas the hormone must act on all the cells that eventually form the mesenchymal condensation. Mesenchyme of the mammary region only is competent to produce this testosterone response. All the mesenchymal cells required for the reaction are already present at the epithelial surface at least 2 days before the hormone response occurs, and our experiments exclude the participation of any cells that could have arrived at the mammary bud through migration from more distant sites.