Endocrine Abstracts

Introduction: Leptin is a pro-inflammatory cytokine and excess leptin in obesity may induce autoimmune disease. The suppressors of cytokine signalling (SOCS) are negative regulators of cytokine signalling and therefore a target for therapy. SOCS3 modulates leptin actions but there is no data regarding other SOCS proteins and leptin signalling.Aim: To develop a bioassay and examine the actions of SOCS proteins on leptin signalling.M...

Introduction: Leptin modulates immune activation in relation to nutritional state and there is gender difference in body composition and the immune response. Leptin induces the release of pro-inflammatory cytokines, including TNF-alpha, from human peripheral blood mononuclear cells (PBMCs). We hypothesised that estrogen may modulate the immune actions of leptin. Aim: To test the effect of estrogen on leptin signalling and leptin-induced TNF-alpha production. Materials and Meth...

The adrenal steroid dehydroepiandrosterone (DHEA) is the most prominent circulating steroid in humans and is also a precursor for sex steroids in peripheral tissues. In prostate, DHEA is a substrate for two major metabolic pathways that produce antagonistic sex steroids. In one pathway, DHEA is converted into potent 5alpha-reduced androgens such as 5alpha-dihydrotestoterone (DHT) and thus shares with testicular androgens the control of prostate growth and functions in both nor...

IntroductionOvulation involves rupture of the ovarian surface, and thus the ovarian surface epithelium (OSE) is subjected to serial injury and repair with each ovulatory cycle. Inflammation is integral to the process of ovulation, but importantly, inflammatory damage is also thought to be a potential mechanism of ovarian tumour development. We have examined OSE responses to an inflammatory stimulus associated with ovulation, Interleukin-1alpha (IL1alpha)...

Background: The majority of patients with GH insensitivity have defects in the extracellular domain of the GHR. We have identified a 47yr old woman homozygous for a 22bp deletion in the cytoplasmic domain of the GHR. The patient had high GH levels, and low IGF-1 of 8 ug/L (normal 54-389 ug/L), IGFBP-3 16nmol/L (normal 61-254 nmol/L) and GHBP 6.8 percent (normal greater than 10 percent) levels. We report functional studies for this mutation (GHR1-449) which results in premature...

We have previously reported dominant negative missense mutations (P467L, V290M) in human PPAR gamma (peroxisome proliferator-activated receptor gamma) in association with severe insulin resistance, early onset type 2 diabetes and hypertension. In a large UK kindred, where the proband presented at age 15 years with severe insulin resistance (acanthosis nigricans, hyperinsulinaemia, PCOS), we have identified a novel heterozygous frameshift premature stop mutation in the PPAR gam...

Background: Management of CAH involves replacing cortisol deficiency and reducing raised adrenal androgens, however the supraphysiological glucocorticoid doses often required to treat hyperandrogenism are associated with poor long-term health outcomes. Modified-release hydrocortisone (MRHC) capsules, Efmody, replicate cortisol diurnal rhythm and improve control of CAH compared to standard glucocorticoid therapy. Here we report changes in glucocorticoid daily dose and 9am 17-hy...

Background: Current glucocorticoid replacement regimens for patients with primary adrenal insufficiency (PAI) mean patients wake with either low or undetectable cortisol levels1, associated with fatigue and a reduced quality of life (QoL)2. Plenadren® (Takeda, UK) is a once-daily modified-release formulation of hydrocortisone that replaces daytime cortisol levels whereas Chronocort® (modified-release hydrocortisone hard capsules, Diurnal, UK) wh...

Background: Adrenal crisis is the leading cause of excess mortality in patients with CAH1. Retrospective studies report an adrenal crisis incidence of 5-10/100 patient years (PY), with mortality 0.5/100 PY2. Modified-release hydrocortisone (MRHC) capsules, (Efmody), replicate cortisol diurnal rhythm and improve androgen control in CAH compared to standard glucocorticoid therapy2. Here, we report the incidence of adrenal crisis in CAH patients f...