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摘要
Chronic stress as well as major depressive disorders is associated with cortisol metabolism. Two enzymes modulate cortisol (F) and cortisone (E) interconversion: 11 beta-hydroxysteroid dehydrogenase type 1 and type 2 (11 beta-HSD1 and 11 beta-HSD2). Furthermore, F and E were inactivated by 5 alpha and 5 beta reductases to their tetrahydro-metabolites: tetrahydrocortisol (THF), allo-tetrahydrocortisol (5 alpha-THF) and tetrahydrocortisone (THE). To better understand depression a LC-MS/MS method for simultaneous determination of F, E THF, 5 alpha-THF and THE in human urine has been developed and validated. The quantification range was 0.1-160 ng mL(-1) for F and E, and 0.2-160 ng mL(-1) for the tetrahydro-metabolites, with >86.1% recovery for all analytes. The nocturnal urine concentrations of F, E and tetrahydro-metabolites in 12 apparently healthy male adult volunteers and 12 drug-free male patients (age range, 20-50 years) with a diagnosis of depression were analyzed. A series of significant changes in glucocorticoid metabolism can be detected: F/E ratios and (THF+5 alpha-THF)/THE ratios as well as F and THF concentrations were significantly higher in depression patients than in healthy subjects (p<0.05); 5 alpha-THF/F ratios, 5 alpha-THF/THF ratios as well as 5 alpha-THF concentrations were significantly lower in depression patients (p < 0.05). The results pointed to the decreased 11 beta-HSD2 activity and a dysfunction in the 5 alpha-reductase pathway in depressed patients. This method allows the assessment of 11 beta-HSD1/2 and 5 alpha/beta-reductase activities in a single analytical run providing an innovative tool to explain the potential etiology of depression.
- 出版日期2015-3-25
- 单位华中科技大学
