Orexins/hypocretins increase the promoter activity of selective steroidogenic enzymes.
Orexins (hypocretins) regulate multiple physiological functions, including central regulation of energy homeostasis and sleep-wake behavior but also peripheral hormonal actions. Recent data suggest specific effects of orexins at adrenal glands. To further assess the mechanism by which orexins regulate steroidogenesis we analyzed the effect of orexin A and B on the transcriptional activity of the luciferase reporter gene driven by the human steroid 21-hydroxylase (CYP21), 3β-hydroxysteroid dehydrogenase (HSD3B2), 11β-hydroxylase (CYP11B1), and aldosterone synthase (CYP11B2) gene promoter regions. After transient transfection of the reporter gene constructs into human NCI H295R cells, treatment with orexin A and B for 6 and 12h increased the promoter activity of the CYP11B2, HSD3B2 and, to a lesser extend, CYP21 genes. The activity of the CYP11B1 was increased by both orexins after 3h of treatment. Compared to the effects of forskolin or angiotensin II, however, the effect of orexins on the transcriptional activity of the steroidogenic enzyme genes was moderate. Our results suggest that orexins increase the expression of steroidogenic enzymes at the transcriptional level and that orexins play a role in the long term regulation of adrenal steroid production.
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Sonja M
SM
Kagerer
Christine
C
Eichholz
Olaf
O
Jöhren
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D017930:Genes, Reporter; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D000068797:Orexins; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins