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Mesenchyme-mediated Effect of Testosterone on Embryonic Mammary Epithelium¹

Institut für Molekularbiologie der Österreichischen Akademie der Wissenchaften, Billrothstr. 11, A-5020 Salzburg, Austria

The embryonic mammary rudiment of the mouse responds to testosterone with the formation of a condensation of mesenchymal cells around the gland bud and subsequent necrosis of the gland epithelium. Experimental 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 further that association of mammary epithelium with "mammary" 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 interaction is discussed in regard to its possible significance for an androgen therapy of metastatic breast cancer (i.e., mammary epithelium in nonmammary mesenchyme).

¹ Presented at the John E. Fogarty International Center Conference on Hormones and Cancer, March 29 to 31, 1978, Bethesda, Md. Supported by National Cancer Institute Contract N01-CB-33883.

² Present address: Anatomisches Institut der Universität Göttingen, West Germany.