钙通道阻滞剂对原代培养醛固酮产生腺瘤细胞类固醇激素谱的影响

doi:10.16352/j.issn.1001-6325.2022.11.1656

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (11): 1656-1660.doi: 10.16352/j.issn.1001-6325.2022.11.1656

钙通道阻滞剂对原代培养醛固酮产生腺瘤细胞类固醇激素谱的影响

高寅洁¹, 禹松林², 尹逸丛², 崔云英¹, 张玉石³, 邱玲², 童安莉^1*

中国医学科学院北京协和医学院北京协和医院 1.内分泌科国家卫生健康委员会内分泌重点实验室;
2.检验科疑难重症及罕见病国家重点实验室;
3.泌尿外科,北京 100730

收稿日期:2022-05-05 修回日期:2022-06-29 出版日期:2022-11-05 发布日期:2022-11-01
通讯作者: ^* tonganli@hotmail.com
基金资助:
国家自然科学基金(81770427,82070822)

Effect of calcium channel blocker on steroid hormone profile of primary cultured aldosterone producing adenoma cells

GAO Yin-jie¹, YU Song-lin², YIN Yi-cong², CUI Yun-ying¹, ZHANG Yu-shi³, QIU Ling², TONG An-li^1*

1. Department of Endocrinology,Key laboratory of Endocrinology of National Health Commission;
2. Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases;
3. Department of Urology, Peking Union Medical College Hospital, CAMS & PUMC, Beijing 100730, China

Received:2022-05-05 Revised:2022-06-29 Online:2022-11-05 Published:2022-11-01
Contact: ^* tonganli@hotmail.com

摘要/Abstract

摘要： 目的探究钙通道阻滞剂(CCB)维拉帕米对原代培养醛固酮产生腺瘤细胞类固醇激素谱的影响。方法对北京协和医院伴有低钾血症的6例醛固酮产生腺瘤(APA)手术患者的肿瘤组织进行原代培养,以不同浓度的维拉帕米处理。用液相色谱-串联质谱(LC-MS/MS)检测细胞培养液中类固醇激素谱。结果维拉帕米 50 μmol/L组醛固酮水平低于维拉帕米 10 μmol/L组,且低于对照组(P＜0.01)。维拉帕米 10 μmol/L组的醛固酮前体物质11-脱氧皮质酮水平低于对照组(P＜0.05)。维拉帕米 50 μmol/L组和维拉帕米10 μmol/L组的18-氧-皮质醇(18-OXOF)和18-羟-皮质醇(18-OHF)水平均低于对照组(P＜0.05)。此外,维拉帕米对糖皮质激素如皮质醇和可的松、肾上腺来源性激素如硫酸脱氢表雄酮(DHEA-S)和11-羟-睾酮(11-OHT)也存在一定的抑制作用。结论 CCB药物除了能够抑制原代培养APA 细胞的醛固酮分泌外,对其他多种类固醇激素,如醛固酮前体物质11-脱氧皮质酮、皮质醇以及代谢产物18-OXOF和18-OHF均有显著的抑制作用。

关键词: 醛固酮产生腺瘤, 类固醇激素谱, 醛固酮, 18-氧-皮质醇, 18-羟-皮质醇

Abstract: Objective To explore the influence of calcium channel blocker(CCB), verapamil, on steroid hormone profile of primary cultured aldosterone producing adenoma(APA)cells. Methods The adrenal tumor tissues of 6 APA patients with hypokalemia operated in Peking Union Medical College Hospital were cultured and treated with different concentrations of verapamil. The steroid hormone profile was detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS). Results The level of aldosterone in 50 μmol/L verapamil group was lower than that in 10 μmol/L verapamil group and control group(P＜0.01). The levels of aldosterone precursor, 11-deoxycorticosterone in verapamil 10 μmol/L group was lower than that in control group (P＜0.05). The levels of 18-oxocortisol(18-OXOF) and 18-hydroxycortisol(18-OHF) in verapamil 50 μmol/L group and verapamil 10 μmol/L group were lower than that in the control group (P＜0.05). In addition, verapamil also had some inhibitory effects on glucocorticoids such as cortisol and cortisone, and adrenal derived sex hormones such as dehydroepiandrosterone sulfate(DHEA-S) and 11 beta-hydroxytestosterone(11β-OHT). Conclusions In addition to inhibit-ing aldosterone secretion in primary cultured APA cells, CCB has significant inhibitory effects on a variety of other steroid hormones, such as precursor 11-deoxycorticosterone, cortisol, metabolites, 18-OXOF and 18-OHF.

Key words: aldosterone producing adenoma, steroid hormone profile, aldosterone, 18-oxocortisol, 18-hydroxycortisol

中图分类号:

R586.9

高寅洁, 禹松林, 尹逸丛, 崔云英, 张玉石, 邱玲, 童安莉. 钙通道阻滞剂对原代培养醛固酮产生腺瘤细胞类固醇激素谱的影响[J]. 基础医学与临床, 2022, 42(11): 1656-1660.

GAO Yin-jie, YU Song-lin, YIN Yi-cong, CUI Yun-ying, ZHANG Yu-shi, QIU Ling, TONG An-li. Effect of calcium channel blocker on steroid hormone profile of primary cultured aldosterone producing adenoma cells[J]. Basic & Clinical Medicine, 2022, 42(11): 1656-1660.

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钙通道阻滞剂对原代培养醛固酮产生腺瘤细胞类固醇激素谱的影响

Effect of calcium channel blocker on steroid hormone profile of primary cultured aldosterone producing adenoma cells

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