Under the influence of hormones, the mammary gland undergoes marked developmental changes during pregnancy to express its differentiated function during lactation and thereafter involutes to become developmentally dormant. Previous studies show that the lactogenic hormones stimulate transcription of milk protein genes by inducing phosphorylation of specific transcription factors such stat5. Our goal is to identify genes and characterize their function that are involved in the hormonal regulation of growth and differentiation of the mammary gland. During the course of our study, we have discovered a transcription-activating factor for the murine selenocysteine tRNA gene( mStaf). The selenocysteine tRNA is essential for the biosynthesis of selenoprotein that are thought to have a vital function in the gland. Subsequently we found that the lactogenic hormones regulate the level of mStaf transcript and selenoproteins such as iodothronine deiodinase I and II in the mammary gland. As an extension of our studies of genes encoding seleno-protein in mammary tissue, we examined the regulation and possible functional importance of another selenoprotein, the glutathione peroxidase family including Gpx1,2,3 and 4. These enzymes play a major role in protecting cells from oxidative injury by reducing the hydroheroxides and maintaining the redox status. Our present study revealed that Gpx2 expression in the mammary tissue underwent developmental alterations whereas the other Gpxs, 1, 3 and 4 remained constant. The expression of Gpx2 was low in the glands of virgin, pregnant and lactating mouse whereas an increased expression occurs during the early stage of involution, during which period an oxidative surge occurs in the gland. The treatment of mammary cells with pro-oxidants increased the level of Gpx2 transcript but had no effect on the other Gpxs in vitro culture system. In addition, these agents induced apoptosis only in cells having a relatively lower level of Gpx2 activity. Moreover, enhancement of Gpx2 activity by treating with glucocorticoid, anti-inflamatory steroid or by transfecting those cells with a Gpx2 construct increased their resistance to the action of pro-oxidants on apoptosis. These results suggest that Gpx2 is involved in the cell survival and apoptosis in development and regeneration of the mammary gland. We are currently examining this view by conducting experiments using Gpx gene knock-out mice.
