Endocrine Abstracts

Glucocorticoids possess potent angiostatic properties. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) amplifies local glucocorticoid action in a tissue-specific manner, and we have shown that inactivation of this enzyme enhances angiogenesis within sponges implanted subcutaneously, wounds and infarcted myocardium. 11βHSD1 is present within ocular tissues but its role in the pathogenesis of proliferative retinopathy is unknown. We hypothesised that inhibition ...

The hyperparathyroidism-jaw tumour (HPT-JT) syndrome, an autosomal dominant disorder, is characterised by the occurrence of parathyroid tumours, often carcinomas, and ossifying fibromata of the jaw. The HPT-JT gene, referred to as HRPT2, is located on chromosome 1q25 and consists of 17 exons that encode a 531 amino-acid protein designated parafibromin. To explore the role of HRPT2 in parathyroid tumourigenesis, we generated two mouse models that comprised a conve...

Background: Women with polycystic ovarian syndrome (PCOS) tend to have a cluster of several coronary risk factors, including atherogenic dyslipidaemia. Metformin has been used to improve their hyperandrogenism and to induce ovulation. However, its effects on hyperlipidaemia are less clear and it is not known if metformin also ameliorates lipid intrinsic variability.Aim: The primary end point of the study was to evaluate the effects of metformin and a hyp...

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. Over 95% of MEN1 patients will have developed a manifestation of MEN1 by the age of forty years, and in >85% of patients, parathyroid tumours are the first to occur. In a previously reported Men1 knockout mouse model, parathyroid tumours occurred in less than 50% of Men1 heterozygous (Men1+/−...

Neuroendocrine tumours are slow growing and could be mistaken for other more malignant tumours with poorer prognosis. Their secretory profile may alter with time. The importance of awareness of these tumours and their clinical behaviour is illustrated by the case of a 78-year-old woman who presented with recurrent fasting hypoglycaemia.The patient had been diagnosed with metastatic pancreatic adenocarcinoma a year previously on the basis of radiographic ...

Pituitary tumours occur in more than 40% of multiple endocrine neoplasia type 1 (MEN1) patients, and these are more aggressive and difficult to treat than those in non-MEN1 patients. Assessments of in vivo proliferation rates will be of importance in evaluating emerging treatments. We have used the uptake of the DNA nucleotide precursor, 5-bromo-2-deoxyuridine (BrdU), to assess proliferation rates of pituitary tumours in our Men1 knockout mouse model, which devel...

Objective: Rimonabant has been shown to reduce weight, free androgen index (FAI) and insulin resistance in obese patients with PCOS compared to metformin. Metformin has also been shown to maintain the weight loss and enhance the metabolic and biochemical parameters achieved by treatment with rimonabant. We have determined the effect of rimonabant on the incretin hormones in patients with PCOS.Design: A randomized open labelled parallel study of metformin...

Topical glucocorticoid therapy causes adverse effects in human skin including a reduction in dermal fibroblast proliferation and extracellular matrix protein secretion (e.g. collagen 1) and epidermal thinning – effects paralleled in photoexposed and elderly skin. These cause reduced wound healing rates and a loss of elasticity with increased fragility and transepidermal water loss – signs also typical of Cushing’s syndrome characterised by raised circulating cor...

Retinoic acid (RA) acts as an anti-proliferative and re-differentiation agent in the therapy of thyroid carcinoma but the molecular mechanisms by which RA mediates these effects are not well understood. We have investigated the effect of RA on the production and post-translational modification of the two ENO1 transcriptional products in the human follicular thyroid carcinoma cell line FTC-133. The single ENO1 transcript encodes a 48 kDa ENO1 with its unique N-terminal enolase ...

CD38 is an enzyme which catalyses the production of the second messengers cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate which mobilize calcium from ryanodine-sensitive intracellular calcium stores. Intracellular calcium is well known to be important for mobilisation of secretory granules to the plasma membrane in preparation for exocytosis and CD38 signalling has recently been demonstrated to increase posterior pituitary oxytocin release (Jin et al.</i...