Endocrine Abstracts

Introduction: We previously reported the novel finding that leptin, and several other fat-derived hormones (adipokines), is expressed and regulated in rat hypothalamus (1). Subsequently leptin (ob) mRNA was found in human, sheep and pig brain, but was surprisingly undetectable in mouse brain. In the present experiments we used a mouse hypothalamic neuronal cell line to investigate possible inhibitory mechanisms that may prevent mouse neurons from expressing ob mRNA. These incl...

Background: The UK acromegaly register reported that <60% of acromegalics on medical therapy had controlled disease (1). This is because many patients do not respond to somatostatin therapy. Pegvisomant, a growth hormone antagonist (GHA), controls disease in >95% cases, but is not cost-effective and requires high dose daily injections (2). There is therefore an unmet need for a cost-effective GHA. We have developed a fusion technology for making a cost-effective long-a...

Introduction: The hypothalamic kiss1/kisspeptin system is pivotal in controlling fertility. However, kiss1 transcripts were also quantified in rat fat, where expression was regulated by oestradiol (Brown et al. 2008) and by dihydrotestosterone (DHT; Brown et al. 2009). In human fat, microarray analysis revealed abnormal, multiple gene expression in obese PCOS patients (Corton et al. 2007). In the present experiments we used a rat model (Manne...

The epidemic-like increase in obesity in young people is paralleled by a rise in related diseases such as PCOS, especially in pubertal girls. Kisspeptins, encoded by the KiSS1 gene, are firmly linked with the normal control of the reproductive system and loss-of-function mutations are associated with absence of puberty. Although KiSS1 is predominantly expressed in the hypothalamus (HYP), we detected KiSS1 mRNA in rat pituitary (PIT) and adipose tissue (FAT...

Resistin is a newly-described hormone whose expression in adipose tissue is regulated by fasting, insulin and obesity. We recently reported that resistin mRNA is also expressed in mouse hypothalamus and pituitary (FEBS Letts. 526, p26 (2002)). In the present study we hypothesized that adiposity would influence hypothalamic resistin immunoreactivity (ir). Two different, polyclonal antisera ( raised against aa 51-108, human ; aa 83-91, mouse ) revealed resistin ir in coronal sec...

Background: Parathyroid hormone (PTH) is a peptide hormone consisting of 84 amino acids with residues 1–34 responsible for its biological activity. Hypoparathyroidism is a rare, complex condition with a patient predisposition toward impaired mineral homeostasis. Replacement with Natpara (PTH 1-84) requires daily injections and is still complicated by fluctuating calcium levels. An unmet need exists for a long-acting treatment that is effective. It is hypothesised that a P...

Rationale: Over the last 20 years, granulocyte colony-stimulating factor (GCSF) has become a recognized therapy in the treatment of patients suffering from neutropenia. Current therapies require daily injections of GCSF to stimulate stem cell production and response to treatment is often unpredictable as GCSF is rapidly cleared. A number of approaches to reducing GCSF clearance have been tried mainly through conjugation with another moiety. The technologies already being emplo...

Introduction: Adipokines, such as resistin and fasting-induced adipose factor (FIAF), are implicated in the regulation of insulin sensitivity and regulated by nuclear receptors like peroxisome proliferator activated receptor gamma (PPARγ), and retinoic acid receptor alpha (RARα). Primarily expressed in murine fat, we also showed that these adipokines are expressed in the mouse hypothalamus, as well as in N-1 hypothalamic neurons. We hypothesized that rosiglitazone (R...

In previous work we demonstrated that various adipokines, including leptin and resistin, were expressed in the hypothalamus and anterior pituitary gland. We hypothesized that a practical approach to investigate the putative central role of such factors would be to selectively silence gene expression by RNA interference (RNAi). We tested this hypothesis using model in vitro systems : C6 glioblastoma cells , which we reported express leptin, and 3T3-L1 adipocytes which are known...

Vascular calcification is a regulated process with similarities to osteogenesis, however, the precise mechanism underlying this process is poorly understood. Pericytes are pluripotential microvascular cells which have been shown to differentiate along an osteogenic lineage. Glucocorticoids are widely prescribed drugs but have adverse side-effects including both vascular lesion formation and bone loss. The mechanism underpinning the contrasting effects of dexamethasone (dex) on...