The aim of the present work was to study the influence of variable stress on the expression of 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and the neuropeptides corticotropin-releasing hormone (CRH), urocortins 2 and 3(UCN2, UCN3), arginine vasopressin (AVP), oxytocin (OXT) and adenylate cyclase-activating polypeptide (PACAP) in two inbred rat strains: stress hypo-responsive Lewis (LEW) and hyper-responsive Fisher 344 (F344) rats. We found site-specific and strain-dependent differences in the basal and stress-stimulated expression of 11HSD1, CRH, UCN2, UCN3 and PACAP. In LEW rats, stress upregulated 11HSD1 in the prefrontal cortex and lateral amygdala, whereas in F344 rats 11HSD1 was upregulated in the central amygdala and hippocampal CA2 and ventral but not dorsal CA1 region; no effect was observed in the paraventricular nucleus, pituitary gland and adrenal cortex of both strains. The expression of glucocorticoid receptors did not parallel the upregulation of 11HSD1. Stress also stimulated the expression of paraventricular OXT, CRH, UCN3 and PACAP in both strains but amygdalar CRH only in LEW and UCN2/UCN3 in F344 rats, respectively. The upregulation of PACAP and CRH was paralleled only by increased expression of PACAP receptor PAC1 but not CRH receptor type 1. These observations provide evidence that inbred F344 and LEW rats exhibit not only the well-known phenotypic differences in the activity of the HPA axis but also strain- and stress-dependent differences in the expression of genes encoding 11HSD1 and neuropeptides associated with the HPA axis activity. Moreover, the differences in 11HSD1 expression suggest different local concentration of corticosterone and access to GR in canonical and noncanonical structures of the HPA axis.
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 1 genetika metabolismus MeSH
- amygdala metabolismus MeSH
- arginin vasopresin genetika metabolismus MeSH
- hipokampus metabolismus MeSH
- hormon uvolňující kortikotropin genetika metabolismus MeSH
- hypofýza metabolismus MeSH
- hypofyzární adenylátcyklázu aktivující peptid genetika metabolismus MeSH
- krysa rodu rattus MeSH
- kůra nadledvin metabolismus MeSH
- messenger RNA metabolismus MeSH
- mozek metabolismus MeSH
- nucleus paraventricularis hypothalami metabolismus MeSH
- oxytocin genetika metabolismus MeSH
- potkani inbrední F344 MeSH
- potkani inbrední LEW MeSH
- prefrontální mozková kůra metabolismus MeSH
- psychický stres genetika metabolismus MeSH
- receptory glukokortikoidů genetika metabolismus MeSH
- stanovení celkové genové exprese MeSH
- systém hypofýza - nadledviny metabolismus MeSH
- systém hypotalamus-hypofýza metabolismus MeSH
- urokortiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- MeSH
- autistická porucha genetika MeSH
- lidé MeSH
- myši MeSH
- neuropeptidy fyziologie genetika MeSH
- oxytocin fyziologie genetika MeSH
- serotonin fyziologie genetika MeSH
- synapse fyziologie patologie MeSH
- testosteron fyziologie genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
Novel sites of oxytocin receptor expression have recently been detected in central nervous system, cardiomyocytes, endothelial cells, various carcinoma cells, etc. These and other discoveries have greatly expanded the classical biological roles of oxytocin, which are stimulation of uterine smooth muscle contraction at parturition and milk ejection during lactation. It is becoming clear that the great diversity of oxytocin actions in the brain and peripheral organs is paralleled by activation of a diversity of signalling pathways. On the other hand, until now only one single oxytocin receptor type has been detected. This receptor belongs to G protein-coupled receptors and in dependence on cell conditions it binds to different G proteins; this phenomenon is called receptor-G protein promiscuity. Thus, in the same cells oxytocin can activate multiple responses at the same time. Recently, the oxytocinergic system has also been implicated in the growth modulation of various neoplastic cells, where it may inhibit or stimulate cell proliferation in dependence on cell type and activated metabolic pathways. The discovery of novel oxytocin receptor-linked signalling cascades brings interesting knowledge opening new avenues for research in oncology and molecular pharmacology with perspectives of finding new therapeutic agents.
- MeSH
- financování organizované MeSH
- inositol-1,4,5-trisfosfát metabolismus MeSH
- lidé MeSH
- nádorové procesy MeSH
- nádory metabolismus patologie MeSH
- oxytocin genetika metabolismus MeSH
- podjednotky proteinů genetika metabolismus MeSH
- proliferace buněk MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- receptory oxytocinu genetika metabolismus MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- exprese genu MeSH
- fyziologický stres patofyziologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- messenger RNA MeSH
- nucleus paraventricularis hypothalami metabolismus MeSH
- oxytocin genetika metabolismus MeSH
- vasopresiny genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
