MODULATION OF CLUSTERIN GENE-EXPRESSION IN THE RAT MAMMARY-GLAND DURING PREGNANCY, LACTATION, AND INVOLUTION

The mammary gland provides an excellent system for investigating facto rs involved in the regulation of epithelial growth, differentiation, m orphogenesis, and involution. We have recently demonstrated that clust erin gene expression is associated with epithelial differentiation and morphogenesis during murine embryogenesis. In the present study, we h ave analyzed expression of clusterin in the rat mammary gland with par ticular emphasis on the periods of pregnancy and lactation. By Norther n blot analysis we show that clusterin mRNA is present in virgin rat m ammary glands, that it is increased during pregnancy and strongly down -regulated during lactation, and that mRNA levels return progressively to those found in virgin rats during the course of involution. Total protein levels, as assessed by Western blot analysis, were also seen t o decrease during lactation. In situ hybridization showed that strong expression of clusterin was localized to epithelial cells of developin g lactiferous ducts and alveoli during pregnancy, and confirmed that e pithelial clusterin expression is down-regulated during lactation. Thi s down-regulation was reproducibly observed in mothers to which pups w ere returned after 2 days of weaning, suggesting that maternal mammary clusterin production is under hormonal control. These results show th at clusterin gene expression is highest in alveolar and tubular epithe lial cells during pregnancy and lowest during lactation, when the prot ein synthetic machinery of differentiated alveolar epithelial cells is devoted to milk production. This suggests that clusterin may be invol ved not only in mammary gland involution but also in the regulation of tubuloalveolar morphogenesis and alveolar epithelial cell differentia tion in the adult rat mammary gland.