Endocrine Abstracts

TSH receptor (TSHR) is a G-protein-coupled seven-transmembrane domain receptor located in the basolateral membrane of thyroid follicular cells. The activated receptor couples to two major signal transductions pathways: the Gs/adenylate cyclase and the Gq/11/phospholipase C signalling. Many loss of function mutations have been identified in this gene leading to a wide spectrum of thyroid abnormalities, ranging from hyperthyrotropinemia and TSH resistance to severe hypothyroidis...

In humans glucocorticoid (GC) excess can promote hepatic glucose and triglyceride production contributing to obesity, fatty liver and diabetes. 11β-HSD1 activates GCs (11-DHC to corticosterone in mice), thereby increasing tissue concentrations. The liver has the highest 11β-HSD1 activity, and its inhibition has emerged as a therapeutic option. To investigate this we generated 11β-HSD1 liver-specific knockouts (HSD1LKO) and examined GC metabolism and responses to...

We report the first case of familial adrenocortical carcinoma (ACC) in association with hereditary non-polyposis colorectal cancer (HNPCC) in a family with a MSH2 germline mutation.HNPCC, an autosomal dominant disorder caused by mutations in one of the DNA mismatch repair (MMR) genes, is the commonest cause of hereditary colon carcinoma, and is associated with an increased risk of certain non-colonic cancers (e.g. endometrial, ovarian, urin...

Meningitis is associated with high mortality and morbidity predominantly driven by meningeal inflammation. Herpes Simplex virus (HSV) is a major cause of viral meningitis typically progressing to HSV encephalitis. Numerous studies highlight the importance of glucocorticoids in lowering inflammation in bacterial meningitis, but very limited data exists on the use of glucocorticoids in viral meningitis. We aimed to characterise 11β-HSD1 (which interconverts inactive cortiso...

5alpha-Reductase1 (5aR1) catalyses glucocorticoid metabolism, potentially modulating glucocorticoid clearance and therefore affecting the activity of the hypothalamic–pituitary–adrenal (HPA) axis. 5aR1 is up regulated in obesity associated with activation of the hypothalamic–pituitary–adrenal (HPA) axis. Here we investigated if inhibition of 5aR1 impairs glucocorticoid clearance and suppresses the HPA axis.Age-matched male and female ...

Objective: Variability in growth hormone (GH) responsiveness is evident in adult hypopituitary patients receiving recombinant GH (rhGH). Doses vary up to 4-fold for unexplained reasons. Deletion of exon 3 in the GH receptor (d3-GHR) has been linked to an increased response to GH treatment in children, although data are conflicting. We investigated the role of the d3-GHR polymorphism in determining GH responsiveness in adult GH deficient patients.Methods:...

Background: There have been a number of drivers that have led nurses to take on extended roles that have been traditionally been the domain of doctors. Competency frameworks for specialist nurses have been developed in other paediatric specialities, such as diabetes, oncology and epilepsy. However, this has not been established for paediatric endocrine nurses.Aim: To establish a competency framework for paediatric endocrine nurse specialists.<p class...

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...

Glucocorticoids mediate the stress response, regulated via the hypothalamic–pituitary–adrenal (HPA) axis. The HPA axis is down-regulated and its responsiveness to stress is impaired in cholestasis. The mechanisms are unknown, but may involve reduced glucocorticoid clearance. Hepatic 5beta-reductase is involved in glucocorticoid inactivation and bile acid biosynthesis. We showed previously that bile acids are potent competitive inhibitors and transcriptional regulator...

Thyroid hormone (T3) is an important regulator of skeletal development and bone turnover. Thyrotoxicosis is associated with accelerated growth, advanced bone age and osteoporosis. T3-action in bone is mediated mainly by T3-receptors (TRs). TRβPV mice harbour a dominant-negative mutation in the TRβ gene that impairs negative feedback control of the hypothalamic-pituitary-thyroid axis resulting in elevated thyroid hormone and TSH concentrations. TRβ<sup...