Endocrine Abstracts

Objective: Three nonsynonomous SNPs, Arg16Gly, Gln27Glu and Thr164Ile, in the coding region of the ADRB2 gene affect either receptor affinity or trafficking. Their distribution has been shown to differ significantly in hypertension. We investigated the association of these loci with hypertension in the Silesian Hypertension Study.Methods: Following local ethics approval, 274 unrelated Polish subjects consisting of 146 hypertensives and 128 normotensives ...

Metyrapone is a potent inhibitor of the conversion of 11-deoxycortisol (11-DOC) to cortisol and is used in the treatment of Cushing's syndrome. This study has assessed the clinical significance of 11-DOC cross-reaction in five serum cortisol assays provided on automated immunoassay analysers. Cross-reaction was determined from the linear regression of increase in measured cortisol against increasing levels of 11-DOC (0, 1590, 4310, 6490, 7040 nmol/L) added to a serum pool. In ...

Background: Functioning gonadotroph adenomas (FGA) are rare benign pituitary tumours. Several case reports suggest that FGA may present with features of ovarian hyperstimulation in women. However, a lack of aggregated clinical experience of FGA precludes the meaningful guidance of management in affected women.Methods: Case series of 7 women presenting at different UK sites with FGA induced ovarian hyperstimulation syndrome (OHSS).R...

Introduction: Our institution leads a UK, multicentre, randomised controlled trial (REVISE-Diabesity ISRCTN00151053) investigating the interaction of Endobarrier therapy, a 60 cm endoscopically implanted proximal intestinal liner, with glucagon-like peptide-1 drug therapy.Aims: To evaluate whether acquired experience could translate into establishment of an effective and safe NHS Endobarrier service in patients with diabesity.Metho...

LH hyper-secretion, driven by increased GnRH pulsatility, underpins excess testosterone secretion – a key clinical feature of PCOS.The kisspeptin-neurokinin B (NKB)-GnRH pathway has emerged as the pivotal regulator of reproduction. We hypothesised that pharmacologic blockade of NKB may address the central pathophysiology of LH hyper-secretion and hyperandrogenism in PCOS. We undertook a randomised, double blind, placebo-controlled multi-centre Phase...

Activation of complement factor 5 (C5) produces the anaphylatoxin C5a and the proinflammatory cytolytic complex C5b-9. Recent studies have shown that C5a receptor (C5aR) deficiency leads to improved systemic and white adipose tissue (WAT) insulin sensitivity. This phenotype is considered to be due to the potent inflammatory potential of signalling through C5aR; however, the pleiotropic functions of C5 in inflammation and metabolism remain to be elucidated. We investigated the ...

Context: Potency of the FSH-pathway varies according to polymorphisms in the promoter of the gene encoding the FSH beta subunit (FSHB −211 G>T, rs10835638) and in the gene encoding the FSH receptor (FSHR 2039 A>G, rs6166). A recent study suggested that carriers of the combination of FSHB GG and FSHR AA had the most reproductive ‘fit’ phenotype (higher serum FSH and a more sensitive FSH receptor). In pre-pubertal girls...

Context: In rodents, in-utero exposure to the exogenous oestrogen diethylstilboestrol (DES) results in reproductive abnormalities in male offspring. It has been proposed that similar anti-androgenic effects also occur in the human fetal testis following oestrogen exposure.Objective: Determine effects of DES exposure on testosterone production by normally growing human fetal testis xenografts.Design: Human fetal testes (15&...

Fetal Leydig cell (LC) dysfunction leads to human male reproductive disorders (‘testicular dysgenesis syndrome’; TDS) that manifest at birth (cryptorchidism, hypospadias) or in young adulthood (low sperm count, testicular germ cell cancer). The factors regulating fetal LC function in early gestation are unknown, but can be disrupted in rats by environmental chemicals (e.g. dibutyl phthalate (DBP)). We identify a novel repressor mechanism that explains this vulnerabil...

Background: Endocrine disruption in the human fetal testis by environmental agents has been proposed as a possible cause of testicular dysgenesis syndrome (TDS) comprising male reproductive disorders such as testicular germ cell tumours (TGCT), cryptorchidism, hypospadias and low sperm counts. Exposure of fetal rats to the widely used plasticizer di(n-butyl) phthalate (DBP) results in a TDS-like syndrome due to a reduction in testosterone production. Whether such effects also ...