Endocrine Abstracts

The melanocortin-2 receptor accessory protein (MRAP) is a type I integral membrane protein that is required for cell surface expression of the melanocortin 2 receptor (MC2R). Mutations in the N-terminal region of this protein are associated with familial glucocorticoid deficiency type II (OMIM#607398).Here we have investigated the expression and biochemical properties of MRAP using polyclonal antibodies to a conserved peptide sequence in the N-terminal r...

FGD is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex to stimulate glucocorticoid production. The disease is caused by mutations in ACTHR or MC2R in 25% of cases, termed FGD type 1, and has previously been linked to a locus on chromosome 8q12.2-21.2 in a single family with FGD type 2. We have recently described a novel gene (FGD2) that when defective is a second cause of FGD. Sequencing of this gene in 100 FGD2 patients ha...

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

Low birth weight infants have higher mortality rates and are at a greater risk of impaired immunity in later life than are their normal-birth-weight counterparts. The aim was to investigate the effect of maternal dietary fat supplementation during the first or second half of gestation on the plasma immunoglobulin A concentration in her offspring.Six pregnant sows were randomly allocated to receive 10% extra energy derived from dietary fat during either t...

The insulin tolerance test (ITT) is used to determine the integrity of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-somatotroph (GH) axes in patients suspected of ACTH and GH deficiency. In adults a cortisol response <500nmol/L is considered pathological and a GH peak <9mU/L is consistent with severe GH deficiency. Exercise is an alternative stimulus to GH release which may be used to diagnose GH deficiency during childhood but is rarely used during adult li...

Thyroid hormone (TH) is essential for fetal development and before 14 weeks maternal supply of TH is critical to the fetus. Subtle abnormalities of maternal thyroid status have been reported to affect neurodevelopment in childhood (1,2). To explore this further, we examined the relationship between maternal thyroid status and newborn measures of growth potential. A cohort of uncomplicated pregnant women (n=480) was recruited. At antenatal booking (mean gestation 13.05 weeks) m...

Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite the absence of structural pituitary defects and normal secretory indices of other pituitary hormones. When tested, there is often no ACTH response to exogenous CRH. Onset may occur in the neonatal period, but often is first observed in later childhood. Candid...

Objective: To construct rat congenic strains to confirm and narrow down a region on rat chromosome 2 previously implicated in blood pressure regulation. To determine expression profiles and identify differentially expressed genes between congenic strain and respective parental strain using microarray technology.Design and Methods: Total RNA was prepared from whole kidney homogenates from 2x parental SHRSPGla and 2x SP.WKYGla2a congenic rats. Expression ...

Introduction: Studies have suggested that PCOS is associated with increased cardiovascular (CVS) risk. The mechanisms that may contribute to increased CVS susceptibility include endothelial dysfunction, vascular inflammation and atherothrombosis.Aim: To compare CVS risk profiles in women with PCOS and healthy age and weight matched controls using novel biochemical and biophysical markers of these pathological processes.Method: Fo...

Patients with obesity are relatively Growth Hormone (GH) deficient. GH has potent effects on adipocyte biology, stimulating lipolysis but also promoting pre-adipocyte proliferation. Conversely, we have shown that cortisol inhibits pre-adipocyte proliferation and enhances differentiation. Furthermore, GH, acting through IGF-1, inhibits 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts the inactive glucocorticoid, cortisone (E) to active cortisol (F) in ad...