High and polarized expression of GLUT1 glucose transporters in epithelial cells from mammary gland: acute down-regulation of GLUT1 carriers by weaning

Abstract

During lactation, the mammary gland shows high metabolic activity, which is dependent at least in part on the availability of glucose. We have studied the regulation of glucose transporter expression in different types of cell in rat mammary gland during the reproductive cycle. Glucose transporter expression varied markedly in the mammary gland during ontogeny. Thus, GLUT1 protein expression increased progressively during pregnancy, reaching the highest levels during lactation. A peak of lactation, GLUT1 protein content, expressed per g issue, was greater in mammary gland than in GLUT1-enriched tissues such as rat brain. In contrast, GLUT4 showed a marked decrease during pregnancy and practically disappeared during lactation. Regardless of the developmental stage, GLUT4 was expressed in adipocytes but not in epithelial cells from mammary gland. On the other hand, GLUT1 was expressed in both cell types. The overall pattern of GLUT1 and GLUT4 expression during the reproductive cycle reflects differences in the cell composition of the mammary gland. Thus, whereas adipocytes predominate before pregnancy, epithelial cells are the main cell type in the mammary gland during late pregnancy and lactation. Immunofluorescence and immunoelectron microscopy indicated that GLUT1 was essentially localized to the basolateral domain of epithelial cells in the mammary gland at peak of lactation, and hardly any labeling was found in the luminal membrane of epithelial cells. GLUT1 expression was acutely regulated in epithelial cells from mammary gland. Thus, GLUT1 protein markedly decreased in lactating rats 24 h after abrupt weaning in the presence of a moderate decrease in GLUT1 mRNA levels. The effect of weaning on GLUT1 protein content was not due to the fall in the plasma concentration of PRL. Thus, bromocriptine treatment for 24 h decreased GLUT1 mRNA levels in the mammary gland, but did not alter the content of GLUT1 protein. Our results demonstrate 1) the existence of a high and polarized expression of GLUT1 glucose transporters in epithelial cells from mammary gland, and 2) that GLUT1 expression is acutely regulated at a posttranslational level by weaning; this is not mimicked by bromocriptine treatment, which rules out PRL as the regulatory factor involved in the effect.