Endocrine Abstracts

The role of oestrogens and androgens on bone metabolism has been studied extensively. However, less is known about the effects of progestins. The progesterone receptor (PR) is expressed in human osteoblasts. Progestins have been found to stimulate osteoblast proliferation, differentiation and growth factor expression (e.g. IGFBP-5) and to increase bone formation. In postmenopausal women progestins combined with oestrogen increased bone density to a greater extent than oestroge...

Generalised and periarticular osteoporosis are common features of inflammatory arthritides. These effects appear due to high levels of pro-inflammatory cytokines. 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) is an intracellular enzyme that generates active cortisol from inactive cortisone and is an important determinant of the effects of glucocorticoids on osteoblasts. In vitro, osteoblastic 11b-HSD1 expression is induced by pro-inflammatory cytokines. We thus ...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor (MR) by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity. We have directly analysed renal 11b...

Studies in rats suggest that androgens are involved in sex-specific differences in blood pressure. In human studies there is no difference in blood pressure between boys and girls, but following puberty, men present with a higher blood pressure than women. Modulation of sodium reabsorption through the ENaC is an important component in the control of sodium balance. This is clearly demonstrated by rare genetic disorders of sodium-channel activity (Liddle's syndrome and pseudohy...

(This poster is based on OC38)...

We report the efficacy, safety, and effects on glucose homeostasis of converting patients with acromegaly from slow release octreotide (OT, treated for >3 months) to pegvisomant (Peg), a GH receptor antagonist. 52 patients (median age 49, range 23-81, 13 with diabetes) who had previously participated in a Peg clinical trial and subsequently treated with OT were enrolled in a 32-week, open-label, multicentre study. Peg 10 mg/d was started 4 weeks after the last dose of OT (w...

The role of 11beta-HSD2 is to provide selective access of aldosterone to the mineralocorticoid receptor by inactivating cortisol. Evidence suggests impaired 11beta-HSD2 activity in some patients with hypertension but also in patients with renal disease where it may contribute to sodium retention, oedema and hypertension. To date these studies have relied upon urinary cortisol metabolite analyses as markers of renal 11beta-HSD2 activity.We have directly a...

A 16-year-old boy was referred to our endocrine unit. He had been diagnosed with constitutional short stature (height <10th centile) aged 11, having not grown well for two years. At that time there were no features to suggest Cushing's syndrome (CS), though he was overweight (BMI 22kg/m2, >90th centile) and bone age was delayed by 2 years. A trial of growth hormone (GH) therapy did not increase growth velocity. By age 15, he was developin...

Fibroblasts are important regulators of local inflammatory responses. These responses are further regulated by tissue glucocorticoid levels. Other stromal lineage cells, adipocytes and osteoblasts, express 11beta-hydroxysteroid dehydrogenases (11b-HSDs) which interconvert inactive cortisone and active cortisol. These enzymes are important regulators of local glucocorticoid levels and their expression is regulated by proinflammatory cytokines. We therefore examined expression o...

Glucocorticoids regulate transcription of many genes through the binding to the glucocorticoid receptor (GR) however, their intracellular levels are tightly regulated by the microsomal enzyme 11beta-hydroxysteroid dehydrogenase. Two isozymes of this enzyme have been cloned and characterised; 11beta- hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which is mainly expressed in the liver and adipose tissue and 11beta-HSD type 2 expressed in the kidney and placenta. Within 2.5kb...