Prolactin-mediated regulation of lipid biosynthesis genes in vivo in the lactating mammary epithelial cell
- 1 June 2011
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 300 (6), E1059-E1068
- https://doi.org/10.1152/ajpendo.00083.2011
Abstract
Prolactin (PRL) is known to play an essential role in mammary alveolar proliferation in the pregnant mouse, but its role in lactation has been more difficult to define. Genetic manipulations that alter expression of the PRL receptor and its downstream signaling molecules resulted in developmental defects that may directly or indirectly impact secretory activation and lactation. To examine the in vivo role of PRL specifically in lactation, bromocriptine (BrCr) was administered every 8 h to lactating mice on the second day postpartum, resulting in an ∼95% decrease in serum PRL levels. Although morphological changes in secretory alveoli were slight, by 8 h of BrCr, pup growth was inhibited significantly. Phosphorylated STAT5 fell to undetectable levels within 4 h. Decreased milk protein gene expression, β-casein, and α-lactalbumin, was observed after 8 h of treatment. To assess mammary-specific effects on lipid synthesis genes, we isolated mammary epithelial cells (MECs) depleted of mammary adipocytes. Expression of genes involved in glucose uptake, glycolysis, pentose phosphate shunt, de novo synthesis of fatty acids, and biosynthesis of triacylglycerides was decreased up to 19-fold in MECs by just 8 h of BrCr treatment. Glands from BrCr-treated mice showed a twofold reduction in intracellular cytoplasmic lipid droplets and a reduction in cytosolic β-casein. These data demonstrate that PRL signaling regulates MEC-specific lipogenic gene expression and that PRL signals coordinate the milk synthesis and mammary epithelial cell survival during lactation in the mouse.Keywords
This publication has 44 references indexed in Scilit:
- Sterol regulatory element binding protein and dietary lipid regulation of fatty acid synthesis in the mammary epitheliumAmerican Journal of Physiology-Endocrinology and Metabolism, 2010
- Crystal structure of Spot 14, a modulator of fatty acid synthesisProceedings of the National Academy of Sciences, 2010
- Mammary glands of adipophilin-null mice produce an amino-terminally truncated form of adipophilin that mediates milk lipid droplet formation and secretionJournal of Lipid Research, 2008
- Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactationJournal of Lipid Research, 2003
- Pseudophosphorylated prolactin (S179D PRL) inhibits growth and promotes β-casein gene expression in the rat mammary glandCell and tissue research, 2002
- REGULATION OF MILK PROTEIN GENE EXPRESSIONAnnual Review of Nutrition, 1999
- Activation ofraf-1, MEK, and MAP kinase in prolactin responsive mammary cellsBreast Cancer Research and Treatment, 1996
- Bromocriptine treatment of periparturient goats: long-term suppression of prolactin and lack of effect on lactationJournal of Dairy Research, 1993
- Prolactin Stimulates the Release of Oxytocin in Lactating Rats: Evidence for a Physiological Role via an Action at the Neural LobeNeuroendocrinology, 1991
- Prolactin-mediated transcriptional and post-transcriptional control of casein gene expressionCell, 1979