Endocrine Abstracts

Medial calcification is a major cause of premature cardiovascular mortality in chronic kidney disease. Vascular smooth muscle cells (VSMC) play a key role in this process and studies have suggested a protective role for vitamin D. The exact mechanism for this is unclear but local synthesis of 1,25-dihydroxyvitamin D (1,25D) may be important. Production of 1,25D from 25-hydroxvitamin D (25D) is catalyzed by 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase). 1,25D is metab...

Hypercalcaemia is a prevalent complication in malignancies as a consequence of tumor secretion of parathyroid hormone related peptide (PTHrP). This complication is also associated with ovarian dysgerminomas but is much less common than for other tumours. To investigate this further we have studied 10 cases of dysgerminoma, assessing biochemical parameters and analysing mRNA and protein expression in tissue biopsies. Pathological reports show raised serum calcium and 1,25(OH)<s...

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...

The crucial role of vitamin D in mineral homeostasis is well known. However recent evidence has documented its importance for immunomodulation and inflammation. The kidney is the main source for the endocrine synthesis of the active metabolite 1,25-dihdroxyvitamin D3 (1,25D3), with expression of the key enzyme, 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase). Our aim was to investigate the alteration of the vitamin D hormonal system in renal failure and assess the impact...

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...

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is synthesised by the enzyme 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase). The principal site of 1alpha-hydroxylase activity is in the proximal tubule of the kidney. In order to investigate renal vitamin D metabolism we have used a human proximal tubule cell line, HKC-8. We have previously shown that synthesis of 1,25D3 activity in these cells is sensitive to the concentration of calcium and North...

Homeobox (HOX) genes encode proteins that are important in normal foetal development. Some of these genes such as HOXA10 also appear to be involved in haematopoiesis, tumour invasion and normal uterine function. HOXA10 is sensitively regulated by hormonal changes during the menstrual cycle. In addition, knockout mouse studies have suggested a role for HOXA10 in implantation but its precise mechanism of action remains unclear. To further investigate HOXA10 function in human rep...