Endocrine Abstracts

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin GC mediated changes in insulin signalling are not clear. Within skeletal muscle, the microsomal enzyme, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GC, 11-dehydrocorticosterone (A) to active corticosterone (B) and thus regulates GC availabi...

Stress results in activation of the hypothalamic–pituitary–adrenal axis with increased circulating cortisol. It has been argued that a syndrome of ‘relative adrenal insufficiency’ is common in critically ill patients. Patients who fail to increase their cortisol by >250 nmol/30 min following the administration of 250 μg ACTH in the short synacthen test (SST) have been reported to have a higher mortality (JAMA 2000, 283 1038–1045)...

Congenital adrenal hyperplasia (CAH) caused by mutations in the electron donor enzyme P450 oxidoreductase (POR) is unique amongst all CAH variants in that it can be associated with ambiguous genitalia (disordered sex differentiation, DSD) both in 46,XX and 46,XY individuals. POR has a pivotal role in facilitating electron transfer from NADPH to microsomal P450 enzymes, including CYP17, which catalyses a key step in human androgen synthesis, the conversion of 17-hydroxypregneno...

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotesterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990,335:431; JCE&M 2003,88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previous...

P450 oxidoreductase (POR) has a pivotal role as electron donor to all cytochrome P450 enzymes that are microsomally located, i.e. CYP type II enzymes. Importantly, those include key enzymes involved in glucocorticoid and sex steroid biosynthesis such as CYP17 and CYP21. In addition, the activity of hepatic CYP enzymes involved in drug metabolism and detoxification also crucially depend on the transfer of electrons from NADPH via POR. Recently, mutations in P450 oxidoreductase ...

Aims: To study changes in bone mineral density (BMD), bone mineral parameters, metabolic profile, body composition and quality of life at base line and 6 months following parathyroidectomy, in subjects with primary hyperparathyroidism (PHPT).Material and methods: This prospective study was conducted over 18 months with first 12 months of recruitment and next 6 months for follow-up. Sixty-eight patients with PHPT who underwent surgery were compared with 1...

The causative link between circulating glucocorticoid excess and osteoporosis is established. Although circulating cortisol levels do not change significantly with age, local tissue metabolism may be implicated in age-related bone loss. The enzyme11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) increases local cortisol production, is expressed in human osteoblasts and its activity increases with age leading to a decrease in bone formation. We hypothesised that sele...

In adipose tissue, glucocorticoids (GC) are known to regulate lipogenesis and lipolysis. Hexose-6-phosphate dehydrogenase (H6PDH), a protein located in the endoplasmic reticulum (ER) provides co-factor for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thus regulating the set point of its activity and allowing for tissue specific activation of GCs. The aim of this study was to examine the effect of lack of H6PDH on adipose tissue biology using the H6P...

Background: Non-alcoholic fatty liver disease (NAFLD) is recognized as common liver disorder that represents the hepatic manifestation of the metabolic syndrome including visceral obesity, type 2 diabetes, insulin resistance and hyperlipidemia. Non-alcoholic steatohepatitis (NASH) is the progressive form of liver injury with the risk for progressive fibrosis, cirrhosis and end-stage liver disease. The pathophysiology that leads to NAFLD and NASH is not well understood. We hypo...

Background: Non-alcoholic fatty liver disease (NAFLD) is recognized as common liver disorder that represents the hepatic manifestation of the metabolic syndrome including visceral obesity, type 2 diabetes, insulin resistance and hyperlipidemia. Non-alcoholic steatohepatitis (NASH) is the progressive form of liver injury with the risk for progressive fibrosis, cirrhosis and end-stage liver disease. The pathophysiology that leads to NAFLD and NASH is not well understood. We hypo...