Endocrine Abstracts

Elevated cortisol in Cushing's syndrome or ageing is associated with cognitive dysfunction. 11beta-HSD1 is expressed in rodent hippocampus and frontal cortex, regions important for cognition. In cultured rat hippocampal neurons, 11beta-HSD1 regenerates corticosterone from inert 11-dehydrocorticosterone and its inhibition by carbenoxolone is neuroprotective. 11beta-HSD1 knockout mice are protected against age-related cognitive dysfunction. We hypothesised that in elderly humans...

The hypothalamic melanocortin 4 receptor, its endogenous agonist, alpha melanocyte stimulating hormone and the endogenous antagonist, Agouti related peptide (Agrp) regulate energy homeostasis. However, the physiological role of the hypothalamic melanocortin receptor, MC3-R and its agonist, gamma MSH are currently unknown. We have previously shown that the MC3/4 agonist, a-MSH has no effect on GnRH release from hypothalamic explants and does not influence plasma gonadotrophins ...

CGRP-alpha is a 37 amino acid peptide generated by alternative splicing of calcitonin gene transcripts. CGRP-alpha is present in a number of areas of the brain involved in the regulation of appetite, including the PVN. CGRP(8-37) is a competitive antagonist of CGRP-alpha at the CGRP-type 1 receptor. CGRP-alpha is known to inhibit food intake when given intracerebroventricularly, but the anatomical localisation of this effect is not known. Aims To investigate the effects of CGR...

Pro-opiomelanocortin (POMC) derived peptides coordinate energy balance via central melanocortin receptors. In order to monitor central POMC expression and processing in-vivo, we have quantified the POMC derived peptides ACTH, alpha-MSH and the high molecular weight precursors POMC/proACTH in rat cerebrospinal fluid (csf). POMC/proACTH levels were significantly lower in csf samples from fasted versus fed rats (65.2 ± 4.5 pmol/l versus 112 ± 10.1 pmol/l; p = 0.00...

Annexin I (ANXA1), a Ca2+- and phospholipid-binding protein is an important mediator of glucocorticoid (GC) action in the host defence and neuroendocrine systems. In the anterior pituitary ANXA1 is highly expressed by the folliculo-stellate (FS) cells (1). We have shown that GCs cause the externalization of annexin I in a FS cell line (murine TtT/GF) despite the fact that ANXA1 lacks a signal sequence and is not packaged in secretory granules. In bacteria and yeast ...

The hypothalamic melanocortin system is a regulator of energy homeostasis. Chronic CNS administration of Agouti related peptide (Agrp) causes increased food intake, increased body adiposity, an inhibition of the HPT axis and a suppression of BAT UCP-1. The ability of Agrp to alter oxygen consumption, a measure of energy expenditure, is unknown.Chronic daily ICV administration of Agrp (1nmol) caused a 54% increase in food intake (food intake, day 7: Agrp...

Coordinated interaction between the immune and neuroendocrine systems is of key importance in regulating the host's response to inflammation and anoxic stress. Adenosine, released under such conditions in high concentration, modulates a number of inflammatory processes and can regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis. Although adenosine receptors (ARs) have been described in the pituitary gland, the distribution of the receptor subtypes (A1, A2A, A...

The CNS and gut derived peptide Neuromedin U (NMU) has been shown to inhibit feeding following intracerebroventricular (ICV) injection. The present study aimed to further explore the hypothalamic actions of NMU. ICV NMU-23 (1nmol), but not truncated NMU-8, significantly inhibited feeding (1h food intake: 3.8 plus/minus 0.4g vs saline 5.4 plus/minus 0.6g, p <0.05). Following micro-injection into 8 hypothalamic areas, NMU-23 potently inhibited feeding in the PVN (1h food int...