Endocrine Abstracts

The CRF-related ligand Urocortin 3 (Ucn 3) is expressed in discrete subcortical areas with highest mRNA levels in the medial amgydala (MEA), hypothalamic median preoptic nucleus (MePO) and the rostral part of the perifornical hypothalamic area (PFN). Close anatomical association between major Ucn 3 terminal fields and the type 2-CRF receptor in hypothalamus, lateral septum and medial amygdala suggest it is well placed to modulate physiological processes including behavioural, ...

CRF mediates numerous complementary stress-related endocrine (HPA), autonomic and behavioral responses. CRF antagonists block many stress-induced responses in experimental animals. Furthermore, perturbations of the CRF system or HPA have been reported in human affective disorders. CRF acts through two Class B G protein coupled receptors derived from two genes, which have alternative splice variants and distinct expression patterns. Mice null for CRF-R1 exhibit reduced basal an...

Skeletal muscle is the principal tissue responsible for insulin-stimulated glucose disposal and is thus the major site of peripheral insulin resistance. Urocortin 2 (Ucn2), a corticotropin releasing factor (CRF) family member and the type 2 CRF receptor (CRFR2) are highly expressed in skeletal muscle. To determine the physiological role of Ucn2, we generated mice deficient in this peptide. Using glucose and insulin tolerance tests and hyperinsulinemic euglycemic glucose clamp ...

Chronic exposure to elevated circulating glucocorticoids can lead to metabolic changes, which resemble those observed in Metabolic Syndrome. Features of the Metabolic Syndrome can be reversed by lowering systemic glucocorticoid levels or by treatment with a glucocorticoid receptor antagonist. At the intracellular level, exposure to glucocorticoids is regulated by two distinct 11beta-hydroxysteroid dehydrogenases, 11beta-HSD type 1 and type 2. 11beta-HSD1 predominantly acts as ...

Background: Small bowel neuroendocrine tumors (SBNETs) originate from enterochromaffin cells in the intestine which synthesize and secrete serotonin. Other NETs and other cancers may also produce serotonin but do not store them in vesicles. The rate limiting enzyme of serotonin biosynthesis is tryptophan hydroxylase 1 (Tph1). Patients with high serotonin level could develop carcinoid syndrome, which can be treated with somatostatin analogues and the Tph1 inhibitor telotristat ...