Endocrine Abstracts

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 ...

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...

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body ...

Variation in endogenous glucocorticoid (GC) activity during inflammation has been linked to susceptibility to developing rheumatoid arthritis (RA). It has been shown that in patients with RA inflamed synovial tissue can generate active GCs through the expression of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol. We examined whether the total body activity of 11β-HSD1 or its expression within synovium was assoc...

Acromegaly is associated with increased morbidity and mortality. Surgery, radiotherapy (RT) and medical therapy are the treatment options to decrease GH and IGF-I concentrations to levels associated with cure or normalisation of mortality. We examined the response to dopamine agonists (DA) and somatostatin analogues (SSA) in 276 patients with acromegaly who received medical therapy during follow up (198 DA, 143 SSA). One hundred and seventy two had surgery and 73 RT prior to m...

Polycystic ovary syndrome (PCOS) affects 5–10% of the female population. It is characterised by androgen excess and anovulatory infertility; several studies have reported an increased incidence of the metabolic syndrome and enhanced 5α-reductase activity in PCOS. However, the contribution of obesity to these findings has yet to be clarified. Here we have analysed metabolic status and urinary steroid metabolite excretion in 114 patients with PCOS (median age 30 (range...