Endocrine Abstracts

Objectives and methods: The HORIZON-PFT is a multinational, 3-year, randomized, double-blind, placebo-controlled trial evaluating the potential of once-yearly zoledronic acid (ZOL) 5 mg, infused over 15 minutes, to decrease risk of fracture in 7736 postmenopausal osteoporotic women 65–89 years of age.Results: Treatment with ZOL 5 mg resulted in significant relative risk reductions in morphometric vertebral fracture of 70% vs PBO (3.8% vs 12.8%; 95% ...

The calcium-sensing receptor (CaSR) plays a central role in regulating parathyroid hormone (PTH) secretion in response to changes in extracellular calcium. The CaSR is a G-protein-coupled receptor and ligand binding results in stimulation of phospholipase C (PLC) activity, causing accumulation of inositol 1,4,5-triphosphate (IP3) and the rapid release of calcium ions from intracellular stores. Given the pivotal role of the CaSR in calcium homeostasis, we decided to ...

Steroid receptors are members of a family of ligand-activated transcription factors that mediate tissue responses to a variety of endocrine stimuli. Using the human endometrium as a paradigm of a steroid responsive tissue, we aimed to characterise the expression and function of the oestrogen-receptor related orphan nuclear receptors (ERR) alpha and beta. ERRs share significant sequence homology with oestrogen receptors (ER) alpha and beta but are unable to bind oestradiol. The...

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotesterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990,335:431; JCE&M 2003,88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previous...

Therapeutic glucocorticoids are used in rheumatoid arthritis (RA) to reduce inflammation and bone destruction. We recently reported that primary synovial fibroblasts generate active glucocorticoids via expression of 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1). This enzyme activates cortisol from inactive cortisone (and prednisolone from prednisone) and this activity is up-regulated by inflammation. We have now examined glucocorticoid metabolism in synovial tissu...

Aims: To compare bone mineral density (BMD) and stature between women with androgen insensitivity syndrome and women with gonadal dysgenesis.Settings: Adult Intersex Clinic.Design: Retrospective cross-sectional study of three groups of women aged 17-58 years with varying degrees of exposure to sex hormones and different combinations of sex chromosomes. Forty-six subjects had complete androgen insensitivity syndrome and 46XY [CAIS(X...

The GH receptor antagonist pegvisomant entered clinical trials in 1997 and was (UK) marketed in 2005. There is little long-term experience with this novel drug. We report the experience from two centres that used common protocols to manage 58 patients (36 male, median age 53, range 27 78) since 1997. Before commencing pegvisomant, patients had IGF-I above the upper limit of normal (ULN) of age-related reference ranges (median 1.8 xULN, range 1.2–4.1 xULN) and were uncontr...

Background: A previous study suggested an increased absolute and intraindividual variability of insulin resistance (IR) in overweight women with polycystic ovarian syndrome (PCOS) which may contribute to the increase in cardiovascular risk. There had been no previous data on the change in variability of IR in PCOS with treatment.Methods: PCOS women were recruited using the Rotterdam criteria [mean age (±S.E.M.) 26.4(±1.5)yrs and ...