Glycyrrhizic acid suppresses type 2 11 beta-hydroxysteroid dehydrogenase expression in vivo
Autor: | Hiroyuki Morita, Yukinori Isomura, Tetsuya Tanahashi, Keigo Yasuda, Celso E. Gomez-Sancehz, Tomoatsu Mune, Hiromichi Tanahashi, Hisashi Daido, Tetsuya Suwa |
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Rok vydání: | 2002 |
Předmět: |
Male
medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism Clinical Biochemistry Blotting Western Dehydrogenase Biology Kidney Biochemistry Excretion chemistry.chemical_compound Endocrinology Corticosterone In vivo Internal medicine Microsomes medicine Animals RNA Messenger Rats Wistar Molecular Biology Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Anti-Inflammatory Agents Non-Steroidal Hydroxysteroid Dehydrogenases Kidney metabolism Cell Biology Glycyrrhizic Acid NAD In vitro Rats Dose–response relationship medicine.anatomical_structure chemistry Molecular Medicine 11-beta-Hydroxysteroid Dehydrogenases |
Zdroj: | The Journal of steroid biochemistry and molecular biology. 80(4-5) |
ISSN: | 0960-0760 |
Popis: | Licorice-derivatives such as glycyrrhizic acid (GA) competitively inhibit 11 beta-hydroxysteroid dehydrogenase(11 beta-HSD) type 2 (11-HSD2) enzymatic activity, and chronic clinical use often results in pseudoaldosteronism. Since the effect of GA on 11-HSD2 expression remains unknown, we undertook in vivo and in vitro studies. Male Wistar rats were given 30, 60 or 120 mg/kg of GA twice a day for 2 weeks. Plasma corticosterone was decreased in those given the 120 mg dose, while urinary corticosterone excretion was increased in those given the 30 and 60 mg doses but decreased in those given 120 mg GA. NAD(+)-dependent dehydrogenase activity in kidney microsomal fraction was decreased in animals receiving doses of 60 and 120 mg GA. The 11-HSD2 protein and mRNA levels were decreased in those given 120 mg GA. In contrast, in vitro studies using mouse kidney M1 cells revealed that 24h treatment with glycyrrhetinic acid did not affect the 11-HSD2 mRNA expression levels. Thus, in addition to its role as a competitive inhibitor of 11-HSD2, the chronic high dose of GA suppresses mRNA and protein expression of 11-HSD2 possibly via indirect mechanisms. These effects may explain the prolonged symptoms after cessation of GA administration in some pseudoaldosteronism patients. |
Databáze: | OpenAIRE |
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