Endocrine Abstracts

Background: The CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) genes are found in close proximity on human chromosome 8 and are highly polymorphic, enabling the definition of two common haplotypes. Haplotype1 includes the -344T and the Intron2 conversion polymorphisms in CYP11B2 and also the -1889T, -1859G polymorphisms in the regulatory region of CYP11B1. We and others have shown that these associate with increased aldosterone pr...

Introduction: Strontium ranelate (SR) is a dual action bone agent that increases bone formation and reduces bone resorption. Previous long term studies with SR have demonstrated minimal reductions in parathyroid hormone (PTH) and adjusted calcium (ACa) levels with increase in phosphate (PO4) concentrations, but the exact mechanism of action of SR remains unclear. Postmenopausal women with low bone mineral density (BMD) have relatively high circulating PTH concentrat...

The gastro-entero-pancreatic hormones are involved in the regulation of postprandial nutrient homeostasis. Food intake or fasting triggers the release of these hormones. A direct connection between food intake and bone turnover, assessed by biochemical markers of bone resorption and formation, has been demonstrated in animals and humans.The aim was to study the expression of receptors for the gut hormones, glucose-dependent insulinotropic polypeptide (GI...

Previous studies investigating steroidogenic enzymes in the brain have often focused on only a few genes at a time, using animal models or pooled human RNA to investigate their expression. For this study, we obtained RNA from individual archived human brain tissue samples in order to analyse the transcription of twelve genes involved with steroid biosynthesis and metabolism within the cerebellum and hippocampus.We developed realtime RT-PCR assays for twe...

Background: Aldosterone levels in plasma are reported to be associated with risk of hypertension. Aldosterone secretion from the zona glomerulosa is regulated acutely by the renin/angiotensin system and plasma potassium. The role of ACTH in regulation of aldosterone secretion is disputed.Aim: We have utilised a large population study of middle aged adults to test the extent to which acute aldosterone responses to ACTH are associated with cortisol respons...

Aldosterone is key in the development of hypertension. We have shown that a SNP (−344T) in the 5’ regulatory region (UTR) of the gene encoding aldosterone synthase (CYP11B2) was associated with aldosterone excess and high blood pressure. However, the most robust phenotype is altered adrenal 11-hydroxylation efficiency (deoxycortisol to cortisol); a step carried out by 11β-hydroxylase, encoded by the adjacent gene, CYP11B1. We proposed that the effects of CYP11B...

Introduction: The effect of oestrogens on the male skeleton has been demonstrated in a number of studies and oestradiol (E2) plays an important role in regulating bone mineral density (BMD). The concentration of bioavailable oestradiol (BE), rather than total oestradiol (TE), is associated with bone loss in elderly men.Oestradiol circulates in the bloodstream in one of three forms: bound to SHBG; bound to albumin; and unbound/free. The albumin-bound plus the free fraction comp...

(This poster is based on OC19)...

Bisphosphonates are the treatment of choice for Paget’s disease of bone (PDB). However, long-term effects on complications are unknown. The PRISM trial was a randomised controlled trial comparing symptomatic management and intensive bisphosphonate therapy for PDB, and involved 1324 patients followed for a median of 32 months (range 12–48). Patients allocated to symptomatic therapy (n=663) were untreated unless they had bone pain, at which point they received a...

Introduction: The beneficial effect of GH replacement on bone in AGHD patients is mediated by improvements in target organ sensitivity to PTH and phosphocalcium metabolism. In aging women with established osteoporosis, GH and IGF-1 concentrations are lower and administration of GH has been shown to increase bone turnover and BMD, but the mechanisms remain unclear.Methods: Fourteen postmenopausal women (63.4±2.1 years; mean BMD T score ± ...