Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

详细信息    查看全文

• 作者：Diego F. Cobice ; C. Logan Mackay ; Richard J. A. Goodwin ; Andrew McBride ; Patrick R. Langridge-Smith ; Scott P. Webster ; Brian R. Walker ; Ruth Andrew
• 刊名：Analytical Chemistry
• 出版年：2013
• 出版时间：December 3, 2013
• 年：2013
• 卷：85
• 期：23
• 页码：11576-11584
• 全文大小：441K
• 年卷期：v.85,no.23(December 3, 2013)
• ISSN：1520-6882

文摘

Steroid concentrations within tissues are modulated by intracellular enzymes. Such 鈥渟teroid intracrinology鈥?influences hormone-dependent cancers and obesity and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier transform ion cyclotron resonance mass spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11尾-HSD1. Regional steroid distribution was imaged at 150鈥?00 渭m resolution in rat adrenal gland and mouse brain sections and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11尾-HSD1 deficiency or inhibition, MSI quantified changes in subregional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11尾-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues.