Endocrine Abstracts

Prostanoids have been elucidated as potent adipogenic hormones. Cyclooxygenase (PTGS) is the rate-limiting enzyme of prostanoid biosynthesis and its product, prostaglandin (PG) H2 is a precursor of PGE2, PGF2, PGD2 and PGI2. PGH2 is also metabolised by prostaglandin D-synthase (PTGDS) to PGD2 which spontaneously converts to PGJ2 or can be enzymatically converted to PGF2alpha by AKR1C3. These two metabolites have opposite effect on adipogenesis; PGF2alpha is a PPARgamma antagon...

Glucocorticoids are an important adipogenic factor. In man, circulating cortisol excess causes visceral obesity, but in simple obesity glucocorticoid levels are usually normal. However, in adipose tissue cortisol availability to bind to the glucocorticoid receptor (GR) is modulated by 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1). Human preadipocytes display both dehydrogenase (cortisol to cortisone) and oxo-reductase (cortisone to cortisol) activity. Recent genet...

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

Patients with Cushing's syndrome develop florid, but reversible central obesity. However, circulating cortisol levels are not elevated in simple obesity. Within human adipose tissue, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is highly expressed and converts inactive glucocorticoid, cortisone to active cortisol. Rodents over-expressing 11beta-HSD1 in adipocytes develop central obesity exclusively as a result of increased adipocyte size. Whilst it has ...

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabo...

Central obesity is associated with increased morbidity and mortality. Pre-adipocyte proliferation and differentiation contribute to increases in adipose tissue mass, yet the mechanisms that underpin these processes remain unclear. Patients with glucocorticoid excess develop central obesity, but circulating cortisol levels in idiopathic obesity are normal. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive cortisone (E) to active cortisol (F)...

The enzyme 5β-reductase (AKR1D1) catalyses an essential step in bile acid (BA) synthesis, but in addition, controls intra-cellular steroid hormone availability by inactivation. Steroid hormones and BA are regulators of global lipid and carbohydrate metabolism. As disturbances in steroid hormone and BA metabolism have potent effects on metabolic health, we hypothesize that AKR1D1 may play a role in metabolic homeostasis. The role of AKR1D1 in regulating glucose homeostasis...

Background: We have previously reported abnormal liver function tests (LFTs), FIB-4 scores and liver stiffness measurements (LSM, Fibroscan) in patients with Turner syndrome (TS), but longitudinal data defining the impact of TS on liver phenotype are limited.Methods: We undertook a retrospective longitudinal follow-up audit (OUH; 8348) of 24 women with TS who had abnormal LFTs and underwent at least 2 assessments (median...

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple intrahepatic lipid accumulation to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). 5β-reductase (AKR1D1) is a liver enzyme that catalyses a fundamental step in bile acid (BA) synthesis. Both BAs and BA intermediates are established as potent regulators of metabolic and proliferative phenotype. We have hypothesised that AKR1D1 plays a crucial role in NAFLD and HCC. Human liver b...

Bile acids (BAs) are synthesised from cholesterol in the liver and promote lipid digestion. An emerging body of evidence, however, suggests that BAs are also key signaling molecules with potent metabolic and endocrine functions, exerting their effects through activation of BA receptors, including the farnesoid-X- (FXR) and the G-protein-coupled- (TGR5) receptors. Disturbed BA synthesis has been associated with type 2 diabetes mellitus and insulin resistance, and recent studies...