Endocrine Abstracts

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...

Reproduction requires the temporal and spacial control of specific and exact signals, delivered by locally regulated hormonal flux. In the case of androgen biosynthesis, cytochrome P450 17α-hydroxylase, 17,20-lyase (P450c17) is the key enzyme. However, P450c17 is a multi-functional P450, so, it synthesizes cortisol in the zona fascicula of the adrenal cortex and also androgen precursors in the adrenal zona reticularis and the gonads. The regulation of this dual activity h...

Primary aldosteronism (PA) accounts for the largest proportion of cases of secondary hypertension worldwide. The majority of PA cases are a result of a unilateral aldosterone-producing adenoma (APA). The pathogenesis of APAs, the most curable form of hypertension, has been the focus of worldwide clinical interest, and is associated with mutations in four genes: KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Investigation into these mutations may lead t...

Introduction: Normal pregnancy is characterised by dyslipidaemia which progresses with gestational age as a consequence of the growing energy demands of the mother and developing fetus. Specifically, there is an increase in the maternal plasma cholesterol, triglyceride and phospholipid concentrations.Liver X receptor (Lxr) is a nuclear receptor which promotes cholesterol clearance and de novo lipogenesis.Hypothesis: We hyp...

Aims: MEN1 is characterised by parathyroid, pituitary and pancreatic tumours in association with neoplasia of intra-thoracic endocrine tissue, adrenal glands and cutaneous manifestations. Mutations of the tumour suppressor Menin are causative and affected patients possess heterozygous germline mutations in MEN1, with acquisition of a second hit in the wild-type allele initiating tumourigenesis. Phenotype–genotype correlations can provide insights into the molecular functi...

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder which is associated with higher incidence of gallstone disease. ICP symptoms are usually presented in the third trimester of gestation and their severity advances in parallel with the increase in serum sulphated progesterone metabolites (P4-S) in the mother. Liver X receptor α (LXRα) actively participates in the regulation of lipid metabolism functioning as a cholesterol ...

Glucagon is released from α-cells in the pancreatic islets and is best known for its role in glucose homeostasis. Glucagon/GLP-1 receptor co-agonists have recently been shown to improve glucose homeostasis and reduce body weight in diet-induced obese mice. Glucagon receptor agonism increases energy expenditure while the GLP-1 receptor agonism prevents glucagon-induced hyperglycemia. Peripherally administered glucagon is also capable of reducing food intake, and glucagon n...

We report five cases of hyperthyroidism with complex management issues, which were successfully treated with iopanoic acid prior to thyroidectomy.Three patients (cases 1–3) had Graves’ disease; two developed agranulocytosis on carbimazole and one had uncontrolled severe thyrotoxicosis and poor compliance with treatment. Radioiodine was either declined or contraindicated due to radio-protection issues. All patients were rendered euthyroid with i...

Nuclear receptors control developmental and physiological processes by regulating the transcription of gene networks in specific cells. This is achieved by the recruitment of coactivators and corepressors that lead to chromatin remodelling and alterations in gene transcription. RIP140 is a ligand dependant corepressor for nuclear receptors that plays key roles in adipose tissue and muscle to regulate energy homeostasis.RIP140 regulates carbohydrate and l...

Glucocorticoid (GC) hormone action can be modulated at the pre-receptor level by the endoluminal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1). 11βHSD1 is a bidirectional enzyme that primarily acts as an oxo-reductase in vivo, converting the pro-hormone cortisone to its active form cortisol, while its dehydrogenase activity results in inactivation of cortisol to cortisone. 11βHSD1 oxo-reductase activity allows GC reactivation in a tissue s...