Abiraterone acetate treatment lowers 11-oxygenated androgens.
Abiraterone acetate treatment lowers 11-oxygenated androgens.
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DOI：
10.1530/eje-19-0905
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发表时间：
2020-02
影响因子：
5.8
通讯作者：
Connor Wright;Patrick J O'Day;M. Alyamani;N. Sharifi;R. Auchus
中科院分区：
文献类型：
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作者：
Connor Wright;Patrick J O'Day;M. Alyamani;N. Sharifi;R. Auchus
人类肾上腺是去势抵抗性前列腺癌（CRPC）和经典21-羟化酶缺乏症（21 OHD）雄激素的主要来源。阿比特龙衍生自前药醋酸阿比特龙（AA），可抑制细胞色素P450 17-羟化酶/17，20-裂解酶（CYP 17 A1）的活性，该酶是所有雄激素生物合成所需的酶。AA治疗有效降低21例OHD和CRPC患者的睾酮和雄烯二酮。11-氧合雄激素是主要的肾上腺源性雄激素，但关于AA给药对11-氧合雄激素的影响知之甚少。目的验证AA治疗降低11-氧合雄激素的假设。设计样本分别从AA或AA加泼尼松（AAP）治疗研究的21名OHD或CRPC参与者中获得。方法采用液相色谱-串联质谱法（LC-MS/MS）分别测定6例21 OHD和6例CRPC患者AA或AAP治疗前后血浆或血清中11-氧合雄激素11β-羟基雄烯二酮、11-酮雄烯二酮、11β-羟基睾酮和11-酮睾酮的含量。结果：在CRPC患者中，AAP（1000 mg/d AA+泼尼松和药物去势）的给药将所有四种11-氧合雄激素降低至定量下限以下（较基线降低94%）。在21例OHD患者中，给予AA（100-250 mg/d，持续6天）使所有11种氧合雄激素较基线平均降低56 - 77%。结论：我们得出结论，AA和AAP治疗显着减少肾上腺源性11-氧合雄激素的产生，无论是在高（21 OHD）或正常（CRPC）11-氧合雄激素的患者在基线，分别。11-氧合雄激素的还原是AA和AAP药理学的重要方面。
CONTEXT The human adrenal is the dominant source of androgens in castration-resistant prostate cancer (CRPC) and classic 21-hydroxylase deficiency (21OHD). Abiraterone, derived from the prodrug abiraterone acetate (AA), inhibits the activity of cytochrome P450 17-hydroxylase/17,20-lyase (CYP17A1), the enzyme required for all androgen biosynthesis. AA treatment effectively lowers testosterone and androstenedione in 21OHD and CRPC patients. The 11-oxygenated androgens are major adrenal-derived androgens, yet little is known regarding the effects of AA administration on 11-oxygenated androgens. OBJECTIVE To test the hypothesis that AA therapy decreases 11-oxygenated androgens. DESIGN Samples were obtained from 21OHD or CRPC participants in AA or AA plus prednisone (AAP)-treatment studies, respectively. METHODS We employed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone, and 11-ketotestosterone in plasma or serum samples from six 21OHD and six CRPC patients before and after treatment with AA or AAP, respectively. RESULTS In CRPC patients, administration of AAP (1000 mg/d AA with prednisone and medical castration) lowered all four 11-oxygenated androgens to below the lower limits of quantitation (94% reductions from baseline. In 21OHD patients, administration of AA (100-250 mg/d for 6 days) reduced all 11-oxygenated androgens by on average 56 - 77% from baseline. CONCLUSIONS We conclude that AA and AAP therapies markedly reduce the production of the adrenal-derived 11-oxygenated androgens, both in patients with high (21OHD) or normal (CRPC) 11-oxygenated androgens at baseline, respectively. Reduction of 11-oxygenated androgens is an important aspect of AA and AAP pharmacology.