Endocrine Abstracts

Many glucocorticoid (Gc) actions are of rapid onset, and therefore require acute regulation of intracellular signalling cascades. We have previously identified rapid Gc-dependent activation of the caveolae specific integral membrane protein caveolin, and the cytosolic kinase PKB in the lung epithelial cells, A549.Immunofluorescence studies demonstrate the appearance of activated glucocorticoid receptor (P-ser211-GR) localised to focal points around the c...

Glucocorticoids (Gc) act on most cells and tissues, but their effects vary in a cell-type specific manner. A number of genes show divergent responses to glucocorticoid action, dependent on their tissue of origin. One such gene is MIF, a proinflammatory cytokine associated with Gc resistance in inflammation, and linked with susceptibility to chronic, human inflammatory disease. Importantly, MIF gene expression is inhibited by Gc in lymphoblasts, but not in epithelial cells; a f...

Dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS, have been shown to oppose the effects of glucocorticoids in vivo, thus producing beneficial effects on insulin sensitivity in rodent models of diabetes and obesity as well as in hypoadrenal patients. Glucocorticoids play a key role in regulating fat metabolism and distribution and are reactivated locally by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) oxoreductase activity, which increases with ...

Glucocorticoids (GC) have potent actions upon human adipose tissue, promoting adipocyte differentiation, inhibiting preadipocyte proliferation and inducing lipolysis to generate free fatty acids (FFA) and glycerol through a putative action upon hormone sensitive lipase (HSL). FFA have been strongly implicated in the pathogenesis of insulin resistance, yet the molecular mechanisms that cause GC induced lipolysis are not clear. Recently, several novel lipases have been identifie...

Glucocorticoid (GC) excess is characterized by central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. Whilst it is accepted that GCs cause insulin resistance, both insulin and GCs act synergistically to promote adipocyte differentiation. We have previously shown that GCs cause tissue specific changes in insulin sensitivity, enhancing insulin signalling in human adipose tissue in contrast to muscle.TRB3, a mammalian homolog of <i...

A minority of patients with hyperthyroidism resulting from relapsed Grave’s disease or autonomous nodules refuse definitive treatment with surgery or radioiodine, and request long-term anti-thyroid medication. There are few data concerning the safety and efficacy of this therapeutic modality.We performed a retrospective analysis of 13 patients (8 relapsed Grave’s disease, 5 toxic MNG), 12F, median age 60 (31–76) yrs and duration of long-te...

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...

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among premenopausal women affecting up to 20% of the population. Even though androgen excess is the main diagnostic criterion for PCOS, the evaluation of hyperandrogenemia relies on methods with low accuracy and mainly able to measure total androgen amounts. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) allows high accuracy steroids measurement and if applied to saliva, it also allows the measurem...

The concentrating function of the kidney is important to maintain the water homeostasis of the body. It is regulated by the arginine-vasopressin system through the type 2 vasopressin receptor (V2R). Loss-of-function mutations of V2R in kidney can lead to nephrogenic diabetes insipidus (NDI) which results several symptoms such as polyuria, polydipsia, and hyposthenuria. In this study, we functionally characterized and investigated the potential rescue of a missense mutation (S1...

Introduction: Hypothalamic gonadotropin releasing hormone (GnRH) regulates mammalian reproductive system. It binds receptors (GnRHRs) expressed in gonadotrope cells of anterior pituitary, regulating the synthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). GnRHR is a G protein-coupled receptor (GPCR) coupled to Gαq/11 protein and, to a lesser extent, to Gαi/Gαs proteins, simultaneously activating Ca2+, β-cate...