Endocrine Abstracts

In addition to obesity, models of abnormal hypothalamic melanocortin signalling display increased linear growth, although the mechanism remains unclear. We have studied the somatotrophic axis in the obese agouti (Ay/a) mouse (male, 12-14 weeks), as a model of an altered melanocortin system. Somatotrophic hormones were measured by radioimmunoassay and hypothalamic neuropeptide expression studied by in situhybridisation.Obese A<...

Ghrelin, a circulating gastric hormone, stimulates food intake in rodents and humans and hyperphagia, weight gain and adiposity on chronic administration in rodents. Here we investigated the effect of chronic subcutaneous ghrelin on fat volume and distribution using magnetic resonance imaging (MRI). Male Wistar rats were implanted with subcutaneous osmotic mini-pumps delivering saline (S, n=10) or ghrelin 30nmol/24hours (n=18). In order to investigate the hyperphagia-independe...

The melanocortin receptors (MCR), MC3R and MC4R, have established roles in feeding and pituitary function. MC5R mRNA expression has been identified at low levels in the hypothalamus. However, a role for this receptor in appetite and pituitary function remains to be elucidated. We investigated the effects of central administration of an MC5R agonist (3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2) on food intake and plasma pituitary hormone levels. We did not observe...

Hypothalamic Cocaine- and Amphetamine-regulated transcript (CART) is regulated by circulating glucocorticoids. In adrenalectomised rodents, CART expression is reduced in the arcuate nucleus. However, CART also modulates the hypothalamo-pituitary-adrenal (HPA) axis. Acute intracerebroventricular injection of CART peptide significantly increases plasma ACTH and corticosterone but the long-term actions of CART are unknown. The aim of these studies was to determine the effect of l...

The peptides, cocaine- and amphetamine-regulated transcript (CART), alpha-melanocyte-stimulating hormone (alpha-MSH) and glucagon-like peptide-1 (GLP-1) are present in the circulation and may act as peripheral anorectic signals. CART, alpha-MSH and GLP-1 may play a role in tumour anorexia, but their roles in anorexia nervosa (AN) are unknown. These studies aimed firstly to measure plasma CART, alpha-MSH and GLP-1 in control and AN subjects and secondly, to measure plasma CART ...

Cocaine and amphetamine regulated transcript (CART) was originally isolated from rat brain but CART is also synthesized and stored in the anterior pituitary. The localisation and factors regulating pituitary CART synthesis are largely unknown.Using a specific assay for the pituitary form of CART, CART(55-102), CART-immunoreactivity was detectable in the medium of the corticotroph cell line, AtT-20 (1.73 ± 0.54 fmols per millilitre per 24h) but not in control medium....

The generation of a knockout mouse lacking all POMC-derived peptides by Yaswen et al provided further support for the importance of the melanocortin system in regulating body weight. POMC-null mice have a greater food intake than wild-type littermates on both low fat and high fat diets, resulting in increased body weight. In addition to obesity, these mice have altered pigmentation and defective adrenal development.The hypothalamo-pituitary-thyroid axis (HPT) in the...

Cocaine and amphetamine regulated-transcript (CART) is highly expressed in the hypothalamus and was originally reported to be an endogenous satiety peptide. Intracerebroventricular injection of CART can result in motor abnormalities and recent studies have demonstrated increased food intake after intra-nuclear CART administration. To help clarify the situation CART was over-expressed in the hypothalamus using recombinant adeno-associated virus (rAAV-CART). Recombinant adeno-as...

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...