Endocrine Abstracts

The glucocorticoid (GC) activating enzyme 11β-HSD1 is potently upregulated within macrophages and synovial fibroblasts of inflamed joints, where it increases therapeutic GC signalling and regulates their anti-inflammatory profiles. Whilst in vitro studies have demonstrated the importance of autocrine signalling in this context, the importance of paracrine signalling remains poorly defined. In this study, we examined the role of 11β-HSD1 in paracrine GC signalling bet...

Vitamin D exists as two forms; D3 (UV) and D2 (plant derived). Measuring the metabolite 25-hydroxyvitamin D (25OHD) is routinely applied in research and clinical laboratories to assess vitamin D status. The Institute of Medicine and Society for Endocrinology have previously set recommended vitamin D guidelines based on combined 25OHD3 and 25OHD2 serum concentrations. In order to achieve accurate quantitation of these metabolites, the respective C3 epimers must be separately qu...

In chronic inflammatory disease, an increased proportion of M1 polarised macrophages have been shown to contribute to inflammation and tissue damage through the production of pro-inflammatory cytokines such as TNFα. Previously, we have identified expression of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive glucocorticoids (GCs) to their active counterparts, in M1 polarised macrophages in vivo. We hypothesised that 11β...

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...

Vitamin D metabolites such as 25-hydroxyvitamin D (25D) circulate bound primarily to vitamin D binding protein (DBP). However, for most extra-renal tissues 25D uptake is independent of DBP, even though the ‘free’ 25D fraction is very small. DBP has a lower binding affinity for 25D2 compared to 25D3. We hypothesized that this would increase serum free 25D2, with possible variations in vitamin D function. Mice were placed on diets containing equal amounts (1000 IU/kg) ...

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...

It is well established that the use of therapeutic glucocorticoids to treat inflammatory disease has detrimental effects on bone and we have proposed that these clinical effects are determined by intracellular glucocorticoid generation (inactive cortisone/prednisone to cortisol/prednisolone) by 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1). We have recently shown that glucocorticoids and cytokines are able to act cooperatively to upregulate the action of 11b-HSD1, a fi...

When used to treat inflammatory disease therapeutic glucocorticoids (GCs) cause rapid bone loss. However clinical studies suggest that in patients without inflammation GCs have little impact on the skeleton. The mechanism by which inflammation magnifies the effects of GCs is unknown. We have proposed that intracellular GC generation (inactive cortisone/prednisone to active cortisol/prednisolone conversion) via the 11 beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) enzyme d...

Glucocorticoids (GCs) play a fundamental role in the endocrinology of pregnancy but excess GC in utero may lead to IUGR. Protection against fetal exposure to GCs is provided by the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) located in the placental trophoblast. By contrast, relatively little is known concerning the function of GC-activating 11beta-HSD1 which is expressed within maternal decidua. We have used human deciduas (n=32 first, n=10 second and n=...