Endocrine Abstracts

Polycystic ovary syndrome (PCOS), which affects 7% of the female population, is associated with established cardiovascular risk factors including obesity, dyslipidaemia and insulin resistance. Thrombus formation represents the final step in the atherothrombotic process and clot structure has been shown to predict the predisposition to cardiovascular events. The aim of the present work was to assess the effects of commonly used therapeutic agents on clot structure and fibrinoly...

The IGF-I receptor (IGF-IR) growth/survival pathways are engaged in crosstalk with pathways induced by cell-cell interactions. Different elements of the IGF-IR signalling system also affect the phosphorylation status of molecules involved in the regulation of cadherin-mediated cell-cell adhesion, such as catenins. In addition, the IGF-IR has been shown to co-precipitate with cell adhesion complexes.In this study, the crosstalk between IGF signalling and ...

Igfbp5 is the most conserved of the six members of the Igfbp family, which orchestrate the actions of the insulin-like growth factors (IGFs) systemically via blood and locally within tissues. Igfbp5 is upregulated in key lineages during development (e.g. muscle) and pathologies (e.g. rhabdomyosarcoma).To highlight the range and extent of Igfbp5 actions in vivo, we generated novel lines of transgenic mice t...

IGFBP-5 is the most conserved of a family of high affinity proteins that modulate IGF activity. It is upregulated in key lineages during their differentiation and development. In addition to domains associated with IGF binding, IGFBP-5 also possesses motifs that may be involved with its recently demonstrated IGF-independent actions. We have therefore examined the hypothesis that IGFBP-5 is important during development. We have generated mice overexpressing IGFBP-5 using an ear...

In normal physiology, glucocorticoid receptor (GR) activation regulates cell type-dependent genes whose products influence metabolism, inflammation, cell cycle and apoptosis/cell survival pathways. Synthetic GR agonists, or glucocorticoids (GCs), are often used to treat hematologic malignancies because of GR’s ability to induce proapoptotic gene expression, inhibit nuclear factor–κB, and induce cell cycle arrest. In contrast, recent examination of GR expression ...

Early-stage ER+ breast cancer (BC) with high tumor glucocorticoid receptor (GR) expression is associated with improved long term relapse-free survival compared to tumors with low GR expression. In addition, GR activity inhibits ER-mediated BC cell proliferation. We therefore hypothesized that GR and ER engage in nuclear receptor crosstalk to influence pro-proliferative gene expression, thus contributing to a better outcome in ER+/GR+ breast cancer. To understand the mechanisms...