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...