Endocrine Abstracts

Polycystic ovary syndrome (PCOS) is a clinical triad of anovulation, insulin resistance, and androgen excess. Hyperandrogenism may correlate with metabolic risk but PCOS consensus criteria currently define androgen excess on the basis of serum testosterone only. Here we studied the utility of the androgen precursor serum androstenedione in conjunction with serum testosterone as a predictor of metabolic dysfunction in PCOS.86 PCOS patients fulfilling Rott...

Non-alcoholic fatty liver disease NAFLD has been associated with androgen deficiency, yet in the majority of patients with non-alcoholic steatohepatitis NASH, androgens levels are normal. In contrast, women with polycystic ovarian syndrome PCOS, which is characterised by androgen excess, have evidence of increased liver fat. Our hypothesis is that androgen exposure to the liver may be crucial in the amount of lipid that can accumulate in hepatocytes. C3A human hepatoma cells w...

Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accu...

Glucocorticoids (GC), such as prednisolone, are widely prescribed for their anti-inflammatory and immunosuppressive properties. However, they have significant side-effects including insulin resistance and hepatic steatosis. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts 11-dehydrocorticosterone (11DHC) to active corticosterone (CORT) and thus amplifies local GC action. We hypothesise that enhanced local GC regeneration of exogenously administered GCs by ...

In the pathogenesis of obesity, dysregulated tissue cortisol metabolism (controlled by 11β-HSD1), is postulated to be involved. Fifteen patients (seven mens, mean BMI 50.8±7 kg/m2) awaiting Roux En Y gastric Bypass (RYGB) surgery underwent assessment of 11β-HSD1 activity using cortisol generation profile. Corticosteroids in serum and subcutaneous adipose tissue microdialysis fluid and urinary corticosteroid metabolites were analysed by liquid and gas ...

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...

Background and aims: The mechanisms in HIV by which mitochondrial dysfunction occurs, leading to impaired energy homeostasis and metabolic regulation, are unclear; although similarities are noted in T2DM. Therefore, we investigated the effect of HIV status and ARV therapy on several mitochondrial and nuclear encoded genes related to mitochondrial metabolism and energy homeostasis.Materials and methods: Subcutaneous AT biopsies from the ileac crest were o...

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...

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intrao...

Microsomal glucose-6-phosphatase (G6Pase) and glucose-6-phosphate transporter (G6PT) are key enzymes in regulation of blood glucose concentration. Deficiency of G6Pase gives rise to glycogen storage disease type Ia (GSDIa) whilst mutations in G6PT cause GSDIb. Both are characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly. G6Pase shares its substrate (G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), an ER enzyme functionally coupled with, and which c...