Endocrine Abstracts

The metabolic syndrome, which encompasses features of obesity, insulin resistance, dyslipidaemia and hypertension, has been associated with excessive glucocorticoid (GC) exposure. The pancreas is a target of the adverse affects of GC action, resulting in β-cell damage and reduced glucose-stimulated insulin secretion (GSIS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyses the in vivo conversion of inactive to active glucocorticoids (cortisone E/11-de...

The rate limiting steps of hepatic glucocorticoid clearance are via A-ring reduction by 5α- and 5β-reductases. Our recent in vitro studies suggested that products of 5α-reduction (eg 5α-tetrahydrocorticosterone) can activate glucocorticoid receptors and hence may contribute to glucocorticoid action in liver. Here we compared the effects of administering 5α-tetrahydrocorticosterone (5αTHB) in vivo with those of corticosterone (B)....

Background: A variety of preparations for testosterone replacement therapy are currently available. Testogel, a transdermal gel, is widely used and considered one of the most convenient. Measurement of serum testosterone level at various times after application of the gel is regarded as one of the ways of monitoring response to treatment.Aim: To investigate the variability of testosterone absorption and whether testosterone levels prior to application of...

PPARgamma-agonists improve insulin sensitivity and discourage visceral fat accumulation but mechanisms remain uncertain. In rodents, PPARgamma-agonists downregulate 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in adipose tissue (AT), thereby potentially decreasing intra-adipose glucocorticoid (GC) concentrations. We tested whether PPARgamma-agonists regulate 11b-HSD1 in humans, and if their insulin-sensitising effect is GC-dependent.12 healthy m...

Phaeochromocytomas and paragangliomas arising as part of familial syndromes such as multiple endocrine neoplasia (MEN)2 or von-Hippel Lindau syndrome (VHL) are more likely to be malignant and multiple. Recently the role of mutations in the SDH genes (encoding subunits of succinate dehydrogenase) have also been identified as important in the aetiology of such tumours. We report a case where identification of an apparently sporadic metastatic phaeochromocytoma was found to be co...

In humans, glucocorticoids (GC) are implicated in the pathogenesis of obesity and insulin resistance. GCs are regulated at the prereceptor level by 11beta-hydroxysteroid dehydrogenases (11β-HSD). 11β-HSD type 1 (11β-HSD1) predominantly displays oxo-reductase activity, converting cortisone in man, 11-dehydrocorticosterone in rodents, to cortisol and corticosterone respectively – a reaction requiring the cofactor NADPH. The generation of a hexose-6-phosphate ...

Obesity is associated with decreased hepatic reactivation of glucocorticoids (Gc) by 11β-hydroxysteroid dehydrogenase type 1 (11HSD) and increased metabolism of glucocorticoids by hepatic A-ring reductases, which may contribute to activation of the hypothalamic-pituitary-adrenal axis. Androgen action encourages central obesity and increased metabolic complications, possibly by altering Gc metabolism.This study investigates the role of gonadal androg...

Glucocorticoids (cortisol in man, corticosterone in rodents) can inhibit angiogenesis, alter contractile function and reduce the inflammatory response to injury in the vascular wall. These effects are regulated by the 11beta-hydroxysteroid dehydrogenases (11HSDs) which inter-convert active glucocorticoids and their inactive 11-keto metabolites (cortisone; 11-dehydrocorticosterone) within target tissues. 11HSD2 is a unidirectional, exclusive dehydrogenase which inactivates gluc...

Glucocorticoid excess results in central obesity and insulin resistance/diabetes mellitus. At a pre-receptor level, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) modulates glucocorticoid levels and has been implicated in the pathogenesis of the metabolic syndrome. 11beta-HSD1 is a bi-directional NADP(H) dependant enzyme, but keto-reductase activity predominates in-vivo. Recent studies indicate that the enzyme H6PDH ensures reductive metabolism (cortisone to c...

The NR0B1 (Nuclear Receptor Subfamily 0, group b, member 1) gene, originally called DAX1, encodes an atypical member of the nuclear receptor family. It is proposed to co-regulate other nuclear receptors, repress transcription of downstream gene targets such as steroidogenic factor 1 and play a role in testis development and spermatogenesis. The gene has two exons of 1,168 and 345bp, separated by a 3,385bp intron. It is expressed in the hypothalamic-pitutary-adrenal/gonadal axi...