Endocrine Abstracts

Hypersensitivity of hypothalamic–pituitary–adrenal (HPA) axis is considered to be an important factor in the pathogenesis of depression. Interestingly, glucagon-like peptide-1 (GLP-1) – an incretin hormone involved in the maintenance of glucose homeostasis in the periphery is known to activate HPA axis. The aim of the present study was to investigate whether prenatal stress (an animal model of depression) may influence levels of GLP-1 and GLP-1 receptor (GLP-1R) in the hypothalamus. Since prenatal stress may not change the level of the investigated factors in basal conditions, but may change the response to adverse factors in the adulthood, our studies were also conducted on animals subjected to acute stress and oral glucose administration (1 g/kg). In parallel in order to study the direct influence of GLP-1 receptor agonists on the activity of corticotropin-releasing hormone (CRH) promoter gene, a hypothalamic cell line mHypoA-2/12 was stably transfected with plasmid DNA containing the sequence (from −663 to +124 bp) of human CRH promoter gene conjugated with luciferase reporter gene. The cells were treated with GLP-1 and exendin-4 (20 and 200 nM) for 6, 24 and 48 h. The amount of GLP-1 in the hypothalamus was not altered by prenatal stress in basal conditions, however it was significantly lower in a group subjected to acute stress. Prenatal stress and glucose loading significantly decreased the concentration of GLP-1R in the hypothalamus. Obtained results suggest that attenuated central incretin hormone signaling may contribute to metabolic disturbances, evident in depression. In contrast, transfected mHypoA-2/12 cells treated with selected GLP-1R agonists displayed no significant differences in reporter gene activity, which may suggest that GLP-1R activation does not stimulate CRH expression in this experimental model.

Acknowledgments

This work was supported by the Operating Program of Innovative Economy 2007-2013, grant No. POIG.01.01.02-12-004/09 and grant 2012/07/N/NZ7/04394; National Science Centre, Poland