Glucocorticoids maintain the extracellular matrix of differentiated mammary tissue during explant and whole organ culture

Mouse mammary whole organ culture (WOC) and explant culture of lactating ti ssue were used to investigate the mechanism by which glucocorticoids mainta in secretory epithelium following lobuloalveolar development. The relative number of mammary epithelial cells expressing glucocorticoid receptors did not change with the loss of secretory epithelium during involution as demon strated with competitive binding assays and immunohistochemistry for the gl ucocorticoid receptor. Furthermore, glucocorticoids did not inhibit AP-1 bi nding activity. However, Northern analysis demonstrated that genes associat ed with the breakdown of the extracellular matrix were not expressed in tis sues cultured with glucocorticoids, in contrast to their upregulation durin g involution of mammary tissue cultured with insulin alone. Tissue inhibito r of metalloproteinase-1 (TIMP-1) mRNA expression was lowest in tissue cult ured in the presence of glucocorticoids and increased 2.3-, 3.4-, and 9-fol d when tissues were involuted in the presence of insulin (Ins) alone, Ins a nd hydrocortisone (Hyd) with 0.005 mg/ml, or 0.01 mg/ml collagenase IV, res pectively. These data indicate that glucocorticoids maintain mammary differ entiation in part by inhibiting the turnover of basement membrane.