Endocrine Abstracts

Glucocorticoids are potent anti-inflammatory agents. Endogenous glucocorticoid action is modulated by 11β-hydroxysteroid dehydrogenase (11β-HSD) which interconverts active (cortisol, corticosterone) and intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 regenerates active glucocorticoids. 11β-HSD 1 highly expressed in the lung but its role is little explored.Immunohistochemical staining of mouse ...

Androgen excess is a key feature of the polycystic ovary syndrome; however the molecular mechanisms underlying its pathogenesis largely remain elusive. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant steroid in the human circulation but only unconjugated dehydroepiandrosterone (DHEA) can be converted to active androgens. Conversely, conversion of DHEA to its sulfate ester DHEAS by DHEA sulfotransferase, SULT2A1, diminishes the DHEA pool available for androgen gener...

Recent studies in non-hypertensive patients have shown aldosterone renin ratio (ARR) to be heritable and associated with increased risk of blood pressure (BP) elevation. Furthermore, a raised ARR is present in 10% of hypertensive patients although the precise significance of this is unclear. The magnitude of heritability of ARR will indicate the influence of genetic determination of the phenotype. In this study, we estimated the heritabilities of the components of ARR and the ...

Murine 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses the conversion of inactive 11-dehydrocorticosterone (A) to active corticosterone (B) and plays a key role in metabolic homeostasis. The directionality of this enzyme is dependent upon the presence of NADPH, a cofactor produced by hexose-6-phosphate dehydrogenase (H6PDH). In accord with this, H6PDH KO mice have no reductase and increased dehydrogenase activity of 11βHSD1. Interestingly, H6PDH KO m...

Glucocorticoids possess potent angiostatic properties. 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1) amplifies local glucocorticoid action in a tissue-specific manner, and we have shown that inactivation of this enzyme enhances angiogenesis within sponges implanted subcutaneously, wounds and infarcted myocardium. 11βHSD1 is present within ocular tissues but its role in the pathogenesis of proliferative retinopathy is unknown. We hypothesised that inhibition ...

Adrenal tumours have an incidence of 2–3% in the general population. Adrenocortical carcinoma (ACC), a highly malignant tumor with a poor prognosis, has an annual incidence of two per million but representation in pre-selected patient cohorts with adrenal masses undergoing surgery is up to 12%. Differentiating adrenocortical adenomas (ACA) from ACC represents a continuous challenge, with unfavourable sensitivities and specificities provided by tumour size, imaging criteri...

Background: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex to produce glucocorticoids. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia or overwhelming infection in infancy or childhood. Mutations of the ACTH receptor (melanocortin 2 receptor, MC2R) or the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 & 2 ...

Genes that encode neuropeptides can be recognized in the human genome because their products are (1) highly conserved across species, (2) trafficked though cells by secretory signal peptides and (3) susceptible to proteolytic cleavage at consensus sequences for processing to neuroactive products. One candidate gene is oesophageal cancer-related gene (ECRG4) which was first identified by screening for up- or down-regulated genes in oesophageal cancer. The product of ECRG4, whic...