Growth control and differentiation in mammary epithelial cells.

Growth and differentiation of the mammary gland are controlled by various hormones and other environmental factors. The role of hormones and growth factors in mammary development is discussed with regard to animal species, physiological stages, and the various experimental systems in vitro. In the female embryo, mammary morphogenesis is induced by the mesenchyme and is hormone independent, whereas androgens cause the partial necrosis of mammary epithelium in the male. Ductal growth during adolescence requires estrogen and prolactin or growth hormone. During pregnancy, progesterone participates in the development of the lobuloalveolar structure of the gland. After parturition, changes in the hormonal environment lead to production and secretion of milk. Proliferation and differentiation of mammary epithelium can be induced in culture systems. Insulin and epidermal growth factor (EGF) stimulate mammary cell proliferation in vitro. EGF is required for the optimal growth of the mammary gland during pregnancy. EGF also appears to play an important role in mammary tumorigenesis in certain mouse strains. Production of milk proteins can be induced in vitro by the synergistic interactions of prolactin, insulin, and glucocorticoids and is inhibited by EGF and progesterone. Complete or partial sequencing of several milk protein genes and comparative analysis have led to identification of a sequence of high homology and conservation in the 5' flanking region that is likely to be involved in the regulation of milk protein gene expression.