PARITY-ASSOCIATED CHANGES IN PROLIFERATION, DIFFERENTIATION, ERalpha AND PR EXPRESSION IN THE RAT MAMMARY GLAND

KASS, L.; DURANDO, M; RAMOS, J.G.; VARAYOUD, J.; MUÑOZ-DE-TORO, M.; LUQUE, E.H.

Cincinnati, Ohio, USA

Congreso; 36th Annual Meeting of the Society for the Study of Reproduction.; 2003

In each pregnancy and lactation, mammary epithelial cells proliferate and differentiate. In the present study parity associated changes in markers of proliferation and differentiation were investigated in the rat mammary gland of nulliparous, multiparous non-lactating, and multiparous lactating animals. Mammary glands were obtained on day 9 of first or third pregnancy. Bromodeoxyuridine (BrdU) incorporation, estrogen-alpha (ERalpha) and progesterone (PR) receptors, and alpha-lactalbumin expression were evaluated by immunohistochemistry. Myoepithelial cells were identified using alpha-smooth muscle actin (alpha-SMA) and p63. In multiparous rats, cell proliferation and PR expression in luminal cells were lower whereas alpha-lactalbumin and ERalpha expression were higher than in nulliparous animals. The myoepithelium did not express PR in any group and showed low proliferation index in parous rats. Lactation increased myoepithelial differentiation, while neither the number of myoepithelial cells nor ERalpha expression in these cells was affected in any of the groups studied. The predominant stromal cells type (fibroblasts and adipocytes) did not express PR and showed a minimal rate of BrdU incorporation in all groups. In agreement with results in luminal epithelium, ERalpha expression was higher in the intralobular stroma of multiparous than nulliparous animals. In conclusion, the enhanced expression of alpha-lactalbumin and ERalpha in the multiparous animals is indicative of a different state of differentiation of the luminal compartment. The low proliferative activity of epithelial cells and the high alpha-lactalbumin expression observed in multiparous rats were associated with decreased PR expression. Progesterone acting through its receptor is likely to play a role in proliferative activity modulation and/or differentiation of the mammary gland during gestation that may explain some of the persistent parity associated changes in this organ.