Hyperinsulinemia induces early and dyssynchronous puberty in lean female mice.

Girls with obesity are at increased risk of early puberty. Obesity is associated with insulin resistance and hyperinsulinemia. We hypothesized that insulin plays a physiological role in pubertal transition, and super-imposed hyperinsulinemia due to childhood obesity promotes early initiation of puberty in girls.

PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development.

Background: Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers, and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled.

NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland.

Prior studies have demonstrated that the calcium pump, plasma membrane calcium ATPase 2 (PMCA2), mediates calcium transport into milk and prevents mammary epithelial cell death during lactation. PMCA2 also regulates cell proliferation and cell death in breast cancer cells, in part by maintaining the receptor tyrosine kinase ErbB2/HER2 within specialized plasma membrane domains. Furthermore, the regulation of PMCA2 membrane localization and activity in breast cancer cells requires its interaction with the PDZ domain-containing scaffolding molecule sodium-hydrogen exchanger regulatory factor (NHERF) 1.

Impact of the Variable Killer Ig-Like Receptor-Human Leukocyte Antigen Interactions on Natural Killer Cell Cytotoxicity Toward Foreign CD4 T Cells.

Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions.