Endocrine Abstracts

T3 regulates bone development and its actions are mediated by TRα and TRβ. Using TR knockout mice we demonstrated that TRα1 is the predominant mediator of T3 action in bone, although TRα2 (a non-T3 binding isoform of unknown function) and TRβ1 are also expressed in the skeleton. We show that mice lacking TRα2 have characteristic skeletal abnormalities of delayed closure of the skull sutures, abnormal clavicle development and reduced bone mineraliz...

Previously, we have shown that 5α-tetrahydrocorticosterone (5αTHB), the reduced metabolite of corticosterone (B, the main glucocorticoid in rodents), binds to the glucocorticoid receptor, suppresses the HPA axis but has weak in vivo effects on adipose tissue and liver metabolism. Here we have compared the anti-inflammatory effects of B and 5αTHB in three in vitro and in vivo experiments. Cytokine release was measured by cytometric bead array...

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...

Background: Kisspeptin is a critical regulator of normal reproductive function. In humans inactivating mutations of the kisspeptin receptor GPR54 cause hypogonadotrophic hypogonadism and pubertal failure. Activating mutations of GPR54 cause precocious puberty. Hypothalamic amenorrhoea (HA) accounts for over 30% of cases of amenorrhoea in women of reproductive age. Current treatments have limited success rates and side effects. In rodent models of HA hypothalamic KISS1 expressi...

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite increasing use of GCs as therapeutic agents, the precise molecular mechanisms that underpin GC-induced insulin resistance are unknown. Within skeletal muscle, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to the active GC, cortisol (corticosterone in rodents) and thus amplifies local GC act...

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...

Apart from its role in energy storage, adipose tissue produces several hormones and cytokines termed ‘adipokines’ that have wide-ranging effects on carbohydrate and lipid metabolism; and thereby, play an important role in the pathogenesis of the metabolic syndrome. Visfatin is a novel adipokine, levels of which increase in obesity and is adipogenic; properties common to that of leptin. Thus, leptin may modulate visfatin production in adipose tissue. We investigated t...

Objective: There is evidence that current replacement regimens fail to restore well-being in patients with primary adrenal insufficiency (PAI). Few data is available on QoL in adult male and female patients with CAH.Methods: Patients with CAH or PAI were contacted and received a disease specific questionnaire and three standardized questionnaires (SF-36, GBB-24 and HADS). Reference data for SF-36 scores were obtained from the German National Health Surve...