Endocrine Abstracts

Vascular endothelial growth factors (VEGFs) support angiogenesis and thus tissue growth. They are synthesised and secreted by several cell types but their actions are normally limited to endothelial cells which express VEGF receptors (VEGFRs). Using qRT-PCR and Western blotting we found that normal human thyroid follicular cells also express VEGFRs (VEGFR1-3, neuropilin1 and 2). We have examined the regulation of the expression of VEGFs and PlGFs in the cells. Cells were fully...

We have recently shown that human thyroid follicular cells in culture secrete large amounts of active plasminogen activators (PAs). Thyroid cells also secrete large amounts of vascular endothelial growth factors (VEGFs) and express their receptors, the VEGFRs. PAs, as serine proteases, are known to process growth factors, particularly VEGFs into active forms. In endothelial cells, VEGFs stimulate PA production. We examined the effect of inhibiting VEGF signalling on thyroid fo...

Using qRT-PCR, we found that normal human thyroid follicular cells in culture express the mRNAs for the receptors for vascular endothelial growth factors (VEGFRs). qRT-PCR revealed that the relative production of mRNAs for VEGFRs was neuropilin1=neuropilin2=VEGFR2>VEGFR1 >VEGFR3. Western blotting for phosphoVEGFR2 showed labelling of a 235 kDa protein with few degradation products. VEGFR2 is likely in its active, phosphorylated form, because thyroid cells secrete large...

Human thyroid follicular cells in culture synthesise plasminogen activators, both urokinase (uPA) and tissue-type (tPA). The PAs secreted into the culture medium were active (2.5–50 U/ml) and able to mediate the conversion of plasminogen to plasmin. Secreted PA activity (PAA) was markedly increased by epidermal growth factor (EGF) and protein kinase C (PKC) activation with TPA. There was a corresponding increase in uPA and tPA mRNA levels and in uPA and tPA protein secret...

Vitamin D deficiency is prevalent in pregnant women and associated with adverse pregnancy outcomes, including pre-eclampsia. Active vitamin-D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) appears a key target. Uterine natural killer cells (uNKs) are the most prominent decidual immune cell during early pregnancy. Given their critical role in fetal implantation and placentation, we hypothesised uNKs are a local source...

Vitamin D deficiency is prevalent in pregnant women and associated with adverse pregnancy outcomes, including pre-eclampsia. Active vitamin-D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) appears a key target. Uterine natural killer cells (uNKs) are the most prominent decidual immune cell during early pregnancy. Given their critical role in fetal implantation and placentation, we hypothesised uNKs are a local source...

Vitamin D-deficiency during pregnancy has been associated with increased complications of pregnancy including a high risk of pre-eclampsia (PET). Current analysis of vitamin D ‘status’ is based exclusively on analysis of maternal serum 25-hydroxyvitamin D3 (25(OH)D3), the circulating precursor form of vitamin D. We hypothesised that comprehensive profiling of vitamin D metabolites may provide a more accurate determination of vitamin D function i...

Vitamin D deficiency is prevalent in pregnant women. Active vitamin D (1,25(OH)2D3) exerts important non-classical immune-regulatory effects, and the maternal placenta (decidua) is a potential target for this. CD56+ -uterine natural killer (uNK) cells are the most prominent cell type in the decidua during early pregnancy. Given their critical role in foetal implantation and placentation, we hypothesised that uNK cells are a pivotal immunomodula...

Although a complex metabolic pathway for vitamin D exists, serum measurement of inactive 25-hydroxyvitamin D3 (25OHD3) continues to be the most common determinant of vitamin D ‘status’. However, several other metabolites contribute to the physiological role of vitamin D, notably the active form 1α,25-dihydroxyvitamin D (1α,25(OH)2D3), inactive 3-epi-25OHD3 and chiral 23R and 24R,25(OH)2D3 metabolites. Quantification of these additional metabolites could pro...

Meningitis is associated with high mortality and morbidity predominantly driven by meningeal inflammation. Herpes Simplex virus (HSV) is a major cause of viral meningitis typically progressing to HSV encephalitis. Numerous studies highlight the importance of glucocorticoids in lowering inflammation in bacterial meningitis, but very limited data exists on the use of glucocorticoids in viral meningitis. We aimed to characterise 11β-HSD1 (which interconverts inactive cortiso...