Endocrine Abstracts

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates cortisol (F) from cortisone (E). Our recent human studies identified 11beta-HSD1 to the non-pigmented layer (NPE) of the ocular ciliary epithelium, confirming that this enzyme is integral to the physiology of aqueous humour (AH) production vital for the maintenance of intraocular pressure (IOP). 11beta-HSD1 has also been implicated in the pathogenesis of obesity, and our previous data have defined this enzyme i...

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary ep...

(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...

Childhood obesity is increasing in prevalence and is associated with insulin resistance and Type II diabetes in later life. Site-specific differences in adipose tissue accumulation and associated insulin sensitivity may contribute to these problems.The aims of our study were: 1. To isolate and characterise, subcutaneous (SC) and visceral (V) preadipocytes using small biopsies from pre-pubertal children (ages:4-8years(n=3)) undergoing elective abdominal surgery, with normal...

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...

We hypothesised that normal regulation of 25(OH)D3-24-hydroxylase (encoded by CYP24) determines the autocrine/paracrine action of 1,25(OH)2D3 in normal breast and prostate epithelial cells. Furthermore, these processes are compromised in malignancy.We therefore studied the regulation of CYP24, amongst a panel of breast and prostate cancer cell lines (ZR-75-1, T47-D, MCF-7, MDA-MB-231 breast cells and LNCaP, PC-3 and DU-145 prostate cells) that display d...