Endocrine Abstracts

Background: Dopamine agonists may act on prolactinoma size and secretion through additional effects on adenoma vascularity which can be visualised using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI). To investigate this 23 subjects, 5 with macroprolactinomas (prolactin (PRL) range 14631-500000mU/L), 11 with microprolactinomas (PRL range 621-4777mU/L), 7 individuals with non-lesion hyperprolactinemia and 15 normal volunteers, including 5 females on oral contrac...

Inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) as a means of reducing tissue corticosteroids is showing marked potential as a treatment for type 2 diabetes. However, reduction in tissue corticosteroids may lead to upregulation of the HPA axis. Therefore this study investigates the effect of 11β-HSD1 inhibition on HPA axis biomarkers and examines whether time of dosing impacts on the biomarkers.C57Bl6/Jax mice were fed 60% kcal...

Pro-opiomelanocortin (POMC) derived peptides coordinate energy balance via central melanocortin receptors. In order to monitor central POMC expression and processing in-vivo, we have quantified the POMC derived peptides ACTH, alpha-MSH and the high molecular weight precursors POMC/proACTH in rat cerebrospinal fluid (csf). POMC/proACTH levels were significantly lower in csf samples from fasted versus fed rats (65.2 ± 4.5 pmol/l versus 112 ± 10.1 pmol/l; p = 0.00...

Introduction: The NHS Commissioning Board recommends the introduction of multidisciplinary Tier 3 Specialist Weight Management Services (SWMS) for adults with obesity. Unfortunately, these services are yet to be commissioned in many areas and this largely reflects financial barriers to their development. We have noted, through observation and feedback, that our Tier 3 service is highly valued by patients. Supportive evidence in the literature - although encouraging - is limite...

Glucocorticoids act on several major neuropeptide networks in the hypothalamus which are important for regulation of energy balance and insulin sensitivity. Active glucocorticoids (cortisol/corticosterone in humans/rodents) can be regenerated from their inactive forms by the enzyme 11β-hydroxysteroid dehydrogenase type one (11β-HSD1) which is expressed in the hypothalamus. Therefore we decreased 11β-HSD1 expression in the brain to investigate the role of regener...

Increased corticosterone (cortisol in humans) in liver has important adverse effects on glucose metabolism and is therefore a target for diabetes treatments. The functional effects of corticosterone depend on circulating levels as well as tissue regeneration by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and inactivation by steroid 5-α-reductase type I (5αR). This study investigates how obesity affects diurnal changes in circulating corticosterone, the ge...

Heparan sulphate (HS) is a highly complex linear polysaccharide found attached to core proteins both on the cell surface and in the extracellular matrix. Newly synthesized HS chains are modified by a family of enzymes, many of which have multiple isoforms with differing substrate preferences. These modifications include the addition of sulphate groups at up to four positions on each disaccharide unit. The pattern of modifications a HS saccharide undergoes alters its structure,...

Introduction: Autosomal dominant Kallmann’s syndrome (AKS) results from mutations within the fibroblast growth factor receptor 1 (FGFR1: KAL-2). The FGFR family of tyrosine kinases are involved in a multitude of biological processes from embryogenesis to adult homeostasis. The crystal structure of FGF-FGFR-heparan sulphate (HS) ternary complex has provided a basis for understanding the way in which FGF, FGFR and HS cooperate to assist FGFR dimerization. Anosmin-1, KAL-1 g...

Rationale: Octreotide is known to shrink acromegalic tumours in vivo. However, the mechanism for this is unclear. To investigate the mechanism of shrinkage we used dynamic contrast enhanced MR imaging (DCE-MRI) to visualise the vascular components within the somatotroph adenomas.Subjects & Methods: Six patients with confirmed acromegaly comprising 4 microadenomas (all male) and 2 macroadenomas (1 male, 1 female) were recruited. All patients we...

Endocrine sequelae occur following cancer therapy. The majority of studies focus on childhood survivors of common cancers, in particular brain tumours, and isolated growth hormone deficiency (GHD) following radiotherapy is well recognised. The need for endocrine follow up in adults or following treatment of less common cancers with lower survival rates is often overlooked. Survival following treatment for nasopharyngeal cancer is improving. Although therapy options are changin...