Searchable abstracts of presentations at key conferences in endocrinology

ea0019oc3 | Young Endocrinologist prize session | SFEBES2009

The role of gucocorticoid metabolism in osteosarcoma pathogenesis and treatment

Patel P , Hardy R , Gittoes N , Rabbitt E , Kindblom L , Stewart P , Cooper M

Osteosarcoma (OS) is an aggressive malignant tumour of osteoblasts occurring predominantly in children and young adults. Despite chemotherapy relapse is common and mortality remains ~50%. Non-transformed osteoblasts are highly sensitive to glucocorticoids which reduce proliferation and induce apoptosis. Previously, we observed that OS cells, but not normal osteoblasts, express 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme powerfully inactivates cortis...

ea0019p316 | Steroids | SFEBES2009

Regulation of 11β-hydroxysteroid dehydrogenase type 1 activity in myocytes by differentiation stage, GH/IGF1 and glucocorticoids

Jones CM , Sherlock M , Hardy R , Patel P , Stewart PM , Cooper MS

GH/IGF1 stimulate muscle function whereas excess glucocorticoids induce myopathy. Myocytes express 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme which converts inactive cortisone to active cortisol. GH/IGF-I inhibit 11β-HSD1 expression in some tissues and thus reduce cellular glucocorticoid exposure. This suggests that anabolic actions of GH/IGF1 could be mediated indirectly through effects on 11β-HSD1. The regulation of 11β-HSD1 has be...

ea0011p27 | Bone | ECE2006

Synergistic induction of osteoblastic local glucocorticoid metabolism by inflammatory cytokines and glucocorticoids: a novel mechanism for glucocorticoid-induced bone disease

Kaur K , Hardy R , Stewart PM , Rabbitt EH , Hewison M , Cooper MS

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...

ea0009oc32 | Oral Communication 4: Steroids | BES2005

Differential induction of fibroblast 11beta-HSD1: a mechanism for tissue-specific regulation of inflammation

Hardy R , Cooper M , Filer A , Parsonage G , Buckley C , Stewart P , Hewison M

Acute inflammation plays an important role in the normal immune system by helping to coordinate host responses to danger signals such as infection. In most cases the inflammation is rapidly resolved but in chronic inflammatory diseases such as rheumatoid arthritis (RA) the inflammation persists leading to localized accumulation of potentially damaging immune cells. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that st...

ea0019oc6 | Young Endocrinologist prize session | SFEBES2009

Locally generated glucocorticoids, rather than pro-inflammatory cytokines, directly regulate synovial DKK-1 expression in inflammatory arthritis

Hardy R , Ahasan M , Patel P , Filer A , Rabbitt E , Raza K , Stewart P , Buckley C , Cooper M

We have previously proposed a central role for locally generated glucocorticoids in the periarticular and systemic osteoporosis seen in rheumatoid arthritis (RA). Synovial fibroblasts (SFs) express the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme and this expression increases dramatically with inflammation. Recently, production of DKK-1 (a Wnt signalling inhibitor known to inhibit bone formation) by SFs in response to inflammation has been proposed to ex...

ea0006oc13 | Reproduction | SFE2003

Resistance to insulin-dependent glucose metabolism in human granulosa-luteal cells from anovulatory women with polycystic ovaries

Rice S , Christoforides N , Gadd C , Nickolaou D , Seyani L , Donaldson M , Margara R , Hardy K , Franks S

Insulin resistance and hyperinsulinaemia are well-recognised characteristics of anovulatory women with polycystic ovary syndrome (PCOS) but, paradoxically, steroidogenesis by PCOS granulosa cells remains responsive to insulin. The hypothesis to be tested in this study was that insulin resistance in the ovary is pathway-specific i.e. is confined to the metabolic effects of insulin (i.e. glucose uptake and metabolism) whereas its steroidogenic action remains intact. Granulosa-lu...