title: Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells.
abstract: A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis represents a prominent finding in major depression, possibly related to a dysfunction of the corticosteroid receptor system. Antidepressants are involved in the restoration of the altered feed-back mechanism of the HPA-axis, probably via normalization of corticosteroid receptor functions. Since Hypericum perforatum has antidepressive properties, we here examined its putative actions on glucocorticosteroid receptor mRNA levels in human blood cells as a peripheral model for neuroendocrine effects in human brain cells. Our data show that Hypericum (LI 160) affects the cellular mRNA levels of both, the glucocorticoid receptor (GR)-α and its inhibitory counterpart, the GR-β, at clinically-relevant concentrations. Under these conditions, a bimodal effect was observed. Dose-response studies suggest a rather small effective concentration range and time-effect data show a primary and transient up-regulation of GR-α mRNA levels and a down-regulation of GR-β mRNA levels after 16 h of treatment. The sodium channel blocker benzamil neutralized the effects of Hypericum, pointing to an at least partial mechanism of action via this pathway. In conclusion, Hypericum treatment differentially affects GR-mRNA levels in the human system. Our data suggest a bimodal effect on GR, resulting in a time-and dose-related modification of GR-mediated cellular effects. Such a mechanism has been alleged as an important way of action for a number of antidepressants. It is the first time that a specific effect on both receptors, especially on the subtype of GR-β, is shown under antidepressive treatment in a human system under in vitro conditions.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Rudolf-Bultmann-Str. 8, D-35033 Marburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Enning
authors.forename: H
authors.initials: H
authors.lastname: Murck
authors.forename: J-C
authors.initials: JC
authors.lastname: Krieg
authors.forename: H
authors.initials: H
authors.lastname: Vedder
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002461:Cell Line, Transformed; D003049:Coccidiostats / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D008985:Monensin / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D011987:Receptors, Steroid / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology
chemical_list: D003049:Coccidiostats; C422326:Hypericum extract LI 160; D010936:Plant Extracts; D012333:RNA, Messenger; D011987:Receptors, Steroid; D026941:Sodium Channel Blockers; C013407:benzamil; D000584:Amiloride; D008985:Monensin