PROGESTERONE RECEPTORS IN THE MOUSE MAMMARY DUCT - DISTRIBUTION AND DEVELOPMENTAL REGULATION

During pregnancy, in response to rising levels of estrogen and progest erone, mammary epithelial cells proliferate and differentiate, giving rise to lobulo-alveolar structures from which milk is secreted during lactation. Progesterone, in conjunction with estrogen, also promotes m ammary epithelial growth during puberty, but unlike development during pregnancy, this results in ductal rather than secretory structures. R ecent studies using mice lacking progesterone receptors indicate that these receptors are essential for secretory development. This suggests that during different phases of normal mammary growth and differentia tion, progesterone receptors may mediate their effects through differe nt mechanisms, depending on the physiological state of the animal. The refore, as a prerequisite for understanding the role of progesterone i n normal mammary development, we have investigated the spatial and tem poral distribution of progesterone receptor-containing cells. In the m ammary epithelium of prepubertal mice, high levels of progesterone rec eptor mRNA and protein are present in the actively growing end buds an d ductal branches as well as in the mature duct. Receptor protein was found in some but not in all epithelial cells, and these cells were ch aracterized by large, round, or oval nuclei containing diffuse chromat in. Cytoplasmic and nuclear immunostaining were observed; interestingl y, this staining occurred in separate cells that were in close proximi ty to each other. The relative proportion of cytoplasmic versus nuclea r staining cells changed during pregnancy such that in this developmen tal state, the nuclear staining cells predominated, The potential sign ificance of these observations as they pertain to normal mammary epith elial growth and differentiation are discussed.