Expression of xanthine oxidoreductase in mouse mammary epithelium during pregnancy and lactation: regulation of gene expression by glucocorticoids and prolactin.

In the mammary gland of virgin mice, xanthine oxidoreductase (XOR) enzymic activity is barely measurable. a high increase in the levels of the enzyme is observed during the last days of pregnancy and during lactation, and this is parallelled by an elevation in the amounts of the respective protein and transcript. In situ hybridization experiments demonstrate that the XOR mRNA is specifically expressed in the alveolar epithelial cells of the mammary gland. In HC11 cells, a model culture system for normal breast epithelium, the levels of XOR enzymic activity are dose- and time-dependently induced by dexamethasone, and a further synergistic augmentation is observed in the presence of dexamethasone plus prolactin. Increased XOR gene expression is consequent on glucocorticoid receptor activation, as indicated by sensitivity to the specific receptor antagonist RU486. In addition, the phenomenon is likely to involve protein phosphorylation and dephosphorylation events, as suggested by modulation of XOR mRNA by tyrosine kinase and phosphatase inhibitors.