Endocrine Abstracts

Glucocorticoids are widely prescribed for their anti-inflammatory properties, but have a significant adverse effect profile, leading to a Cushingoid phenotype. In the present study, we test the hypothesis that reactivation of glucocorticoids, in peripheral tissues by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), is a major determinant of exogenous Cushing’s syndrome.WT, global 11β-HSD1 knockout (GKO), liver-specific 11β-HSD...

Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis. The A-ring reductases (5α-reductase type 1 (5αR1) and 2 (5αR2)) generate dihydrotestosterone from testosterone, but importantly also inactivate cortisol and are highly expressed in human liver. We propose that 5αR may regulate GC exposure and therefore may modulate metabolic phenotype in human liver.Primary human hepato...

The 21-hydroxylase (21OH) gene, CYP21A2, encodes the 21OH steroidogenic enzyme which is the primary autoantigen in autoimmune Addison’s disease (AAD). It is located on chromosome 6p21, in a copy number repeat termed RCCX, adjacent to the 21OH pseudogene (CYP21A1P). CYP21A1P is highly homologous to CYP21A2 but contains an 8 bp deletion in exon 3 (707-714delGAGACTAC) which results in a frameshift. The predicted protein product is...

Introduction: There is growing evidence that 11β-HSD1 expression/activity increases with age in key target tissues including adipose tissue, bone, and skin, implicating local amplification of glucocorticoids in the pathophysiology of related disease. We have previously shown that 11β-HSD1KO mice are protected from both the adverse metabolic effects of excess glucocorticoids and age-associated muscle weakness. We investigated changes in global activity and skeletal mu...

Recent genome-wide association studies (GWAS) implicate the CYP17A1 locus in human blood pressure regulation. This gene is important in steroidogenesis, regulating both glucocorticoid and androgen synthesis through catalysis of 17α-hydroxylation and 17,20 lyase reactions. We hypothesised that functional CYP17A1 polymorphisms linked to those identified by GWAS influence blood pressure levels. We therefore screened the entire CYP17A1 locus by dire...

Abdominal surgery and diseases such as endometriosis cause persistent abdominal adhesions leading to pelvic pain, infertility and in severe cases, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (LOX) is a key enzyme required for crosslinking and deposition of insoluble collagen.10–12 weeks old female C57Bl/6 mice (3–10 mice per gro...