Mesenchyme-mediated effect of testosterone on embryonic mammary epithelium.

The embryonic mammary rudiment of the mouse re sponds to testosterone with the formation of a condensa tion of mesenchymal cells around the gland bud and subsequent necrosis of the gland epithelium. Experimen tal combinations of epithelium and mesenchyme of this rudiment, by taking advantage of the androgen-insensitive mutant (Tfm, "testicular feminization"), have shown that the hormone acts directly on the mesenchyme, its effect on the epithelium being indirect and mediated by the surrounding mesenchyme. Only the mesenchymal cells at the epithelial surface are capable of initiating this reaction, and there is no oriented migration of specialized mesenchymal cells to the gland bud in response to the hormone. The mesenchyme forms this condensation only around mammary epithelium; in experimental association the epithelia of the embryonic lung, pancreas, or salivary gland remain unaffected. The experiments suggest fur ther that association of mammary epithelium with "mam mary" mesenchyme must exist for some time before hormone action to allow a response. The finding that the destructive action of testosterone on mammary epithelium is mediated by the surrounding mesenchyme and requires organ-specific tissue interac tion is discussed in regard to its possible significance for an androgen therapy of metastatic breast cancer (i.e., mammary epithelium in nonmammary mesenchyme).