Endocrine Abstracts

Orexins are hypothalamic peptides known to stimulate food intake. Recently, orexins have been shown to activate the HPA axis at a central level1. We have previously shown that during late pregnancy the responsiveness of the HPA axis to a range of stressors is attenuated and suggested that the corticotropin releasing hormone (CRH) neurones or pathways impinging on them are less responsive2. If the CRH neurones themselves are less responsive, they should al...

J was born at term (2.62 kg). She presented aged six months with severe faltering growth, (weight 5.1 kg, length 57.3 cm, OFC 39.0 cm). Investigations showed elevated prolactin (1838 mIU/l) and undetectable IGF1 but were otherwise normal. Her karyotype was 46XX. A brain MRI was normal. By 11 months of age she had evident developmental delay and dysmorphic features (triangular face; hypertelorism; synophrys; broad nasal root; short nose with rounded tip; carp like mouth; short ...

Aims/hypothesis: Resistin could be implicated in the mechanism of insulin resistance and recent evidence suggests this occurs, in part, via a brain-dependent pathway. Given the emerging role of hypothalamic AMP-activated protein kinase (AMPK) in the modulation of appetite and glucose levels, we hypothesized that its activity would be modulated by resistin. To verify such a pathway, we employed the N-1 hypothalamic neuronal cell line, which expresses a variety of neuropeptides ...

Hypoparathyroidism causes severe hypocalcaemia and defective skeletal metabolism. Treatment with calcium and vitamin D supplementation can cause kidney failure whilst native parathyroid hormone (PTH) requires repeated injections and causes renal impairment paralleling high peak and low trough PTH levels. A long-acting PTH, providing constant physiological levels, is needed. LA-PTH, a hybrid of PTH and PTH related peptide, prolongs cAMP responses via altered receptor mechanisms...

Introduction: Leptin is a 16-kDa peptide hormone secreted by adipose tissue and acts as a sensor for energy stores. It feedsback at the hypothalamic arcuate nucleus to suppress appetite. Leptin treatment has been highly effective in suppressing appetite in the rare cases of leptin-deficient obesity and improving the metabolic profile in congenital generalised lipodystrophy. These patients require 2.5–10 mg once daily recombinant leptin treatment. We hypothesised that prol...

Background: The UK acromegaly register reported that <60% of acromegalics on medical therapy had controlled disease (1). Pegvisomant, a growth hormone antagonist (GHA), controls disease in >95% cases, but is not cost-effective and requires high dose daily injections (2). We have developed a fusion technology for making a cost-effective long-acting GH molecule (3), and generated a GHA by linking mutated growth hormone to its binding protein (GHBP).<p class="abstext"...

Background: Acromegaly is associated with increased morbidity and mortality, however currect medical treatment controls the disease in <60% of patients. Pegvisomant, a pegylated GH antagonist, controls the disease in over 95% of cases, but is not cost effective as it requires high dose daily injections and has side-effects. We have developed a technology for generating a long acting potent GH antagonist.Hypothesis: That a GH antagonist fused to GH bi...

Introduction: Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least 1 year after injury, in 25–50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP) to be unrelated to injury severity. Growth hormone deficiency (GHD) and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associate...

Fat-derived adipokine genes that modulate metabolic and inflammatory responses, such as resistin (rstn) and fasting-induced adipose factor (fiaf), are also expressed in mouse brain and pituitary gland. We, and others, reported that central fiaf and rstn mRNA levels were increased following a brain injury-induced inflammatory response, and central injection of resistin reduced food intake and increased hepatic glucose production. Since LPS-induced en...

Introduction: Glycosylphosphatidylinositol (GPI) anchored proteins are common on the surfaces of eukaryotic cells. An example is alkaline phosphatase. Fluorescently Labelled Aerolysin (FLAER) is a bacterial toxin produced by the gram-negative bacterium Aeromonas hydrophila that binds naturally to GPI anchored proteins and utilizes them as receptors to cause cytotoxicity. FLAER has been used to discriminate the GPI deficient red blood cells in cases of paroxysmal nocturn...