title: Prolactin-mediated regulation of lipid biosynthesis genes in vivo in the lactating mammary epithelial cell.
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.
authors.affiliation: Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. steve.anderson@ucdenver.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Rudolph
authors.forename: Tanya D
authors.initials: TD
authors.lastname: Russell
authors.forename: Patricia
authors.initials: P
authors.lastname: Webb
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Neville
authors.forename: Steven M
authors.initials: SM
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001971:Bromocriptine / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D006019:Glycolysis / Q000187:drug effects / Q000235:genetics; D006128:Growth / Q000235:genetics / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D007774:Lactation / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins / Q000096:biosynthesis / Q000235:genetics; D010427:Pentose Phosphate Pathway / Q000187:drug effects / Q000235:genetics; D011247:Pregnancy; D011388:Prolactin / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000254:growth & development; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D006727:Hormone Antagonists; D008055:Lipids; D008894:Milk Proteins; C495678:Slc2a1 protein, mouse; D014280:Triglycerides; D001971:Bromocriptine; D011388:Prolactin