Liquid Chromatography-Tandem Mass Spectrometry Analysis of Human Adrenal Vein 19-Carbon Steroids Before and After ACTH Stimulation

被引:189
作者
Rege, Juilee [1 ]
Nakamura, Yasuhiro [3 ]
Satoh, Fumitoshi [4 ]
Morimoto, Ryo [4 ]
Kennedy, Michael R. [5 ]
Layman, Lawrence C. [2 ]
Honma, Seijiro [6 ]
Sasano, Hironobu [3 ]
Rainey, William E. [7 ]
机构
[1] Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA
[2] Georgia Hlth Sci Univ, Sect Reprod Endocrinol Infertil & Genet, Dept Obstet & Gynecol, Inst Mol Med & Genet,Neurosci Program, Augusta, GA 30912 USA
[3] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 9808575, Japan
[4] Tohoku Univ, Sch Med, Div Nephrol Endocrinol & Vasc Med, Dept Med, Sendai, Miyagi 9808575, Japan
[5] Harbor BioSci Inc, San Diego, CA 92122 USA
[6] Aska Pharma Med Co Ltd, Kawasaki, Kanagawa 2138522, Japan
[7] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
DEHYDROEPIANDROSTERONE-SULFATE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; ANDROGEN EXCESS; CELL-LINE; 11-BETA-HYDROXYANDROSTENEDIONE; EXPRESSION; MARKER; RADIOIMMUNOASSAY; BIOSYNTHESIS; RETICULARIS;
D O I
10.1210/jc.2012-2912
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Abroad analysis of adrenal gland-derived 19-carbon (C-19) steroids has not been reported. This is the first study that uses liquid chromatography-tandem mass spectrometry to quantify 9 C-19 steroids (androgensandtheir precursors), estrone, and estradiol in the adrenal vein (AV) of women, before and after ACTH stimulation. Objective: The objective of this study was to define the adrenal androgen metabolome in women before and after ACTH infusion. Design: This was a retrospective study. Patients: Seven women, aged 50.4 +/- 5.4 years, with suspected diagnosis of an adrenal aldosterone-producing adenoma were included in the study. Methods: AV and iliac serum samples were collected before and after administration of ACTH (15 minutes). AV samples were analyzed using for concentrations of 9 unconjugated C-19 steroids, estrone, and estradiol. Dehydroepiandrosterone sulfate (DHEA-S) was quantified by radioimmunoassay. Results: AV levels of DHEA-S were the highest among the steroids measured. The most abundant unconjugated C-19 steroids in AV were 11 beta-hydroxyandrostenedione (11OHA), dehydroepiandrosterone (DHEA), and androstenedione (A4). ACTH significantly increased the adrenal output of 9 of the 12 steroids that were measured. ACTH increased the mean AV concentration of DHEA-S by 5-fold, DHEA by 21-fold, A4 by 7-fold, and 11OHA by 5-fold. 11 beta-Hydroxytestosterone and testosterone were found to be potent androgen receptor agonists when tested with an androgen-responsive cell reporter model. Conclusion: The current study indicates that the adrenal gland secretes primarily 3 weak androgens, namely DHEA, 11OHA, and A4. Active androgens, including testosterone and 11 beta-hydroxytestosterone, are also produced but to a lesser degree. (J Clin Endocrinol Metab 98: 1182-1188, 2013)
引用
收藏
页码:1182 / 1188
页数:7
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