Endocrine Abstracts

Nuclear pore complexes (NPCs) facilitate the transport of macromolecular cargoes across the nuclear envelope by carrier molecules. The energy for this active transport mechanism is provided by the Ras-family GTPase, Ran, that orchestrates most nuclear trafficking cycles. The RanGEF (RCC1) is located in the nucleus while its GAP is located in the cytoplasm. The nuclear import of steroids, bound to their receptor, is mediated by importins alpha and beta. In the cytoplasm, import...

Endocrinologists focus on circulating and excreted cortisol for diagnosis of, and to assess severity and treatment response in, Cushing’s syndrome (Cs). However, in Cs, morbidity is mediated by excess cortisol binding to intracellular glucocorticoid (GC), mineralocorticoid (MC), and non-genomic receptors. We and others have demonstrated that 11b-hydroxysteroid dehydrogenase type 1 (HSD-1) is the source of about half of intrahepatocellular cortisol in healthy adults, patie...

Glucocorticoids have potent but paradoxical effects on bone. In vitro they are required for the differentiation of osteoblasts but in excess can cause suppression of the mature osteoblast phenotype by reducing proliferation and inducing apoptosis. In vivo, glucocorticoids are anabolic at physiological concentrations, but in excess have an adverse effect on the skeleton most clearly seen in steroid-induced osteoporosis. We have postulated that this paradox may be ...

Background: The adverse effects of corticosteroid therapy are similar to those of endogenous glucocorticoid excess. Previous studies have established the usage patterns of oral corticosteroids in the primary healthcare setting, but these have concentrated on corticosteroid-induced osteoporosis. The aim of this study was to investigate the prevalence and morbidity of long-term oral corticosteroids in a General Practice setting.Methods: From a population ...

Background: Children receiving chemotherapy for ALL may be susceptible to fractures and avascular necrosis (AVN).Aim: To determine the incidence and risk factors for bone-related morbidity in children on ALL chemotherapy.Patients and methods: The medical records of all (n, 186, male: 122) children presenting with ALL between 1997 and 2007 and treated with ALL97/01or UKALL 2003 at one centre were studied. Bone morbidity was d...

Debate surrounds the optimal biochemical assessment in the follow-up of patients withacromegaly, particularly with the introduction of GH receptor antagonists to the treatment algorithm. Consensus statements suggest target values for GH of < 1microgram per litre with normal age and sex matched IGF-1 values. A number of groups have reported on the correlation between IGF-1 and GH levels in small cohorts of acromegalic patients. We retrospectively<p...

Increased mortality in patients with acromegaly has been confirmed in a number of retrospective studies, but causative factors and relationship to serum IGF1 remain uncertain. The West Midlands Acromegaly database contains details of 419 patients (178 males). Serum IGF1 data from the Regional Endocrine Laboratory was available for 338 patients (81%). At diagnosis mean age was 47 years (range 12-84) and mean GH was 70plus/minus5.4 milliunits per litre. 61% were treated by surge...

In humans the most abundant source of 11 beta-hydroxysteroid dehydrogenase type 2 is the placenta, notably placental trophoblast. This enzyme catalyses the conversion of cortisol (F) to cortisone (E) and is thought to protect the fetus from maternal hypercortisolaemia, thereby impacting on fetal growth and development. During gestation placental trophoblast is exposed to dramatic changes in oxygen tensions ranging from ~2% - 12%, changes thought to be pivotal in stimulating an...

Patients with Cushing's syndrome develop florid, but reversible central obesity. However, circulating cortisol levels are not elevated in simple obesity. Within human adipose tissue, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is highly expressed and converts inactive glucocorticoid, cortisone to active cortisol. Rodents over-expressing 11beta-HSD1 in adipocytes develop central obesity exclusively as a result of increased adipocyte size. Whilst it has ...

11beta-hydroxysteroid dehydrogenase type 1 (11B-HSD1) catalyses the inter-conversion of cortisone and cortisol, and has been implicated in the pathogenesis of a number of disorders including insulin resistance and obesity. The enzyme is a glycosylated membrane-bound protein, located in the lumen of the endoplasmic reticulum (ER) and has proved difficult to purify in an active state. Previously, we reported the successful expression and purification of human 11B-HSD1 from E. co...