[Hormonal regulation of the normal mammary gland]

Development and differentiation of mammary gland are controlled by a large number of hormones. In embryo, foetal androgens induce a partial necrosis of mammary epithelium. This action is mediated by cells of the parenchyma which is the real target of androgens. Estrogens are not true growth factor in normal mammary gland: they deliver a message of unknown chemical nature, which allows growth factors to act. The growth factors of mammary cells are only partially known. Clones of the various mammary cell types have been obtained (fibroblasts, adipocytes, myoepithelial and epithelial cells). These clones are a good tool to determine growth factors specific of each cell type. Under the influence of GH, mammary fibroblasts are transformed into preadipocytes which secrete a growth factor (PGE2) which specifically stimulates multiplication of mammary epithelial cells. Other growth factors induced by oestrogens or prolactin have been identified but their exact role remains unknown. Induction of milk synthesis is under the strict dependency of prolactin. The action of this hormone is strongly stimulated by glucocorticoids and insulin at high concentrations and it is inhibited by progesterone and EGF. Prolactin stimulates transcription of milk protein genes and this stimulation is modulated by glucocorticoids and progesterone. Induction of casein and DNA synthesis by prolactin can be mimicked by polyclonal and monoclonal anti-prolactin receptor antibodies. Collagen is necessary for isolated epithelial mammary cells to respond to prolactin signal. The role of other components of the extracellular matrix (proteoglycans, glycoproteins) is partially known. Specific peripheral markers corresponding to the different cell types and to the various stages of mammary gland development have been identified. All these cellular and molecular parameters are compared in normal and tumor mammary cells to point out possible differences.