Endocrine Abstracts

Ghrelin is a circulating growth hormone-releasing and appetite-inducing brain–gut peptide. It needs to be acylated on its serine-3 with octanoate for its endocrine actions. The acyl-transferase that catalyses ghrelin octanoylation has been recently identified and named GOAT (ghrelin O-acyltransferase), which is coded by the MBOAT4 gene. This study aimed to investigate GOAT expression in human. The distribution of GOAT mRNA expression was studied in various human ti...

Introduction: Ghrelin is a potent orexigenic brain-gut peptide with lipogenic and diabetogenic effects, possibly mediated by GHS-R. Cannabinoids also have orexigenic and lipogenic effects. AMPK is a regulator of energy homeostasis and we have previously shown that ghrelin and cannabinoids stimulate hypothalamic AMPK activity while inhibiting it in liver and adipose tissue, suggesting that AMPK mediates both the central appetite-inducing and peripheral effects of ghrelin and ca...

Cushing’s syndrome is characterized by a diverse set of clinical manifestations, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to the metabolic syndrome. AMP-activated protein kinase (AMPK) is an intracellular energy sensor. It integrates nutritional and hormonal signals by switching on catabolic pathways, such as fatty acid oxidation and glycolysis and switching off anabolic pathways, such as fatty ...

We have recently reported that cannabinoids can stimulate hypothalamic and heart AMPK activity and can inhibit liver and adipose tissue AMPK activity in rats (Kola et al., JBC, 2005). These data are in accordance with the known orexigenic and adipogenic cannabinoid effects and also with their beneficial effects on the ischaemic heart. We have studied the effects of cannabinoids on AMPK activity in tissues from wild type (WT) and CB1 knockout (KO) mice to see if the CB1 ...

Cannabinoids and ghrelin exert hypothalamic orexigenic effects and independent peripheral effects have also been reported. We have recently reported that ghrelin and cannabinoids can stimulate hypothalamic and heart AMPK activity, and can inhibit liver and adipose tissue AMPK activity, in rats (Kola et al., JBC, 2005). These data are concordant with the known orexigenic, adipogenic and diabetogenic effects of these compounds as well as with their beneficial effects on t...

Cannabinoids and ghrelin are potent appetite stimulators. The ghrelin receptor (GHS-R1a), endocannabinoids and the cannabinoid 1 (CB1) receptor are expressed in the hypothalamus. There is evidence that the novel CB1 antagonist, rimonabant, causes weight loss by both central and peripheral effects. The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status and regulates the energy metabolism within the single cell but also at whole body level. We have shown p...

Mitogenic signaling by receptor tyrosine kinases that involve increased activity of phosphatidylinositol-3-kinase (PI3K) and over-activation of protein kinase B (PKB/Akt) triggers a cascade of responses that drive tumour progression in a variety of human cancers. Some of these events have been associated with diminished expression of the cell cycle inhibitor p27 through inhibition of a Forkhead transcription factor (FKHR-L1) by Akt, while some others have recently been reporte...

Aim: Clinical acromegaly is characterized by high GH secretion in the presence of high circulating IGF-I levels. We therefore hypothesized that the physiological IGF-I-GH negative feedback loop may be reset in somatotroph adenomas, and we investigated the role of type 1 IGF receptor (IGF-R) and GH receptor (GHR) by quantifying mRNA expression in somatotroph tumours, and investigated the possible presence of mutations of the GHR gene.Methods: Pituitary t...

Background: Ghrelin was recently discovered as the natural ligand for the G protein-coupled growth hormone secretagogue receptor and induces GH release through GHS-R1a. The octanoylation of its third serine residue is responsible for GH release and receptor binding. A variant of ghrelin devoid of this modification, desoctanoyl-ghrelin, can neither bind to the receptor nor induce GH release. Ghrelin has also been shown to effect cellular proliferation, being pro-proliferative i...

The ACTH receptor (ACTH-R) is the second member of the melanocortin receptor family that includes five seven-transmembrane G protein-coupled receptors, and has been shown to be predominantly expressed in the adrenal cortex. It has been postulated that ACTH may regulate its own secretion through ultra-short loop feedback within the pituitary, and as ACTH-secreting adenomas are characterised by resistance to glucocorticoid feedback, they may also have dysregulated ACTH feedback....