**3. The role of E2 and P4 in mammary gland**

The development and physiology of human mammary gland is also under the strict control of steroid hormones, including E2 and P4. The mammary gland is not completely formed at birth, but begins to develop in early puberty when the primitive ductal structures enlarge and branch (Russo et al., 1987). From that point ovarian E2 and P4 are fundamental for the growth and differentiation of the duct system. There are slight cyclical changes during each menstrual cycle caused by ovarian steroid hormones where E2 is increasing the volume of the tissue and P4 is responsible of the acinar growth of breast tissue. During pregnancy, the mammary gland epithelium experiences its greatest and most rapid proliferation initially as a response to the hormones produced by corpus luteum, following by placental hormones.

Due to difficulties in studying developing mammary gland there is relatively small amount of information about normal ER and PR expression in breast tissue. It has been confirmed that PRs and ERs are found in a minority population (7–10%) of luminal, non-dividing epithelial cells. As E2 is required to induce progesterone receptor (PR) expression it is difficult to separate the effects of P4 alone from E2. However, the obligate role of the ERs and PRs in mammary gland development has been confirmed with knocked out mice studies (Bocchinfuso and Korach, 1997; Humphreys et al., 1997).
