دورية أكاديمية
Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism.
| العنوان: | Phenotype-genotype correlation in aldosterone-producing adenomas characterized by intracellular cholesterol metabolism. |
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| المؤلفون: | Harashima S; Department of Pathology, National Hospital Organization Sendai medical center, Sendai, Japan; Department of Pathology, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan., Yamazaki Y; Department of Pathology, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan. Electronic address: y.yamazaki@patholo2.med.tohoku.ac.jp., Motomura N; Department of Pathology, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan., Ono Y; Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan., Omata K; Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan., Tezuka Y; Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan., Morimoto R; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan., Nakamura Y; Division of Pathology, Faculty of medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan., Satoh F; Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan; Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Hospital, Sendai, Japan., Suzuki H; Department of Pathology, National Hospital Organization Sendai medical center, Sendai, Japan., Kwon GE; Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, Korea., Choi MH; Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, Korea., Sasano H; Department of Pathology, Tohoku Graduate School of Medicine, Tohoku University, Sendai, Japan. |
| المصدر: | The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2022 Jul; Vol. 221, pp. 106116. Date of Electronic Publication: 2022 May 06. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Country of Publication: England NLM ID: 9015483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1220 (Electronic) Linking ISSN: 09600760 NLM ISO Abbreviation: J Steroid Biochem Mol Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford ; New York : Pergamon, c1990- |
| مواضيع طبية MeSH: | Adenoma*/metabolism , Adrenal Cortex Neoplasms*/metabolism , Adrenocortical Adenoma*/metabolism , Hyperaldosteronism*/metabolism, Aldosterone/metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics ; Genotype ; Humans ; Lanosterol ; Mutation ; Phenotype |
| مستخلص: | Aldosterone-producing adenoma (APA) is histologically composed of clear and compact tumor cells. KCNJ5- mutated APAs were reported to be associated with higher plasma aldosterone concentration and more abundant clear tumor cells containing lipid droplets than non-KCNJ5- mutated APAs. However, the association among cholesterol uptake and/or synthesis, cellular morphology and genotypes has remained unknown. Therefore, in order to explore these differences, 52 APA cases (KCNJ5 mt: n = 33, non-KCNJ5 mt: n = 19; ATP1A1: n = 3, ATP2B3: n = 3, CACNA1D: n = 5, CTNNB1: n = 1, tumors without any mutation above: n = 7), zona glomerulosa (ZG) tissue adjacent to APA and 10 non-pathological adrenal glands (NAs) were examined for quantitative histopathological analysis of tumor morphology and immunohistochemical analysis of cholesterol receptors (SR-B1, LDL-R), cholesterol metabolic enzymes (ACAT1, ACAT2, HSL, DHCR24, StAR), and the enzymes required for steroid synthesis (CYP11A1, CYP17A, 3βHSD, CYP11B1, CYP11B2). Gas chromatography-mass spectrometry (GC-MS) analysis was further performed to profile cholesterol precursors and metabolites in 21 APA cases (KCNJ5 mt: n = 16, non-KCNJ5 mt: n = 5) and 14 adrenal cortex of adjacent adrenal tissues. Results demonstrated that both SR-B1 and DHCR24 were significantly lower in the ZG than in fasciculata or reticularis of NAs but LDL-R was not significantly different among them in immunohistochemical analysis. SR-B1 and DHCR24 were both significantly higher in APAs than in ZG tissue adjacent to APA. In GC-MS analysis, most cholesterol precursors and metabolites, except for lanosterol, and their metabolic ratios (= concentration of cholesterol/ precursor) were higher in APAs than in the adjacent adrenal cortex tissue. LDL-R, ACAT1/2, HSL, DHCR24 were all significantly lower in clear than in compact tumor cells of APA. LDL-R was significantly lower and cholesterol/lanosterol ratio was significantly higher in KCNJ5- mutated than non-KCNJ5- mutated APAs. We demonstrated SR-B1 mediated selective uptake of cholesterol ester and de novo cholesterol synthesis were both enhanced in APAs. In addition, cholesterol uptake and metabolism were different between clear and compact tumor cells. KCNJ5- mutated APAs were predominantly composed of clear tumor cells containing abundant cholesteryl ester but less activated LDL-R mediated uptake and increased de novo synthesis. Those findings above indicated their more pronounced functional deviation from the normal ZG cells in terms of their steroidogenic and intracellular cholesterol metabolism. (Copyright © 2022 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Aldosterone-producing adenoma; Cholesterol; Immunohistochemistry; KCNJ5; Mass spectrometry; Primary aldosteronism |
| المشرفين على المادة: | 0 (G Protein-Coupled Inwardly-Rectifying Potassium Channels) 0 (KCNJ5 protein, human) 1J05Z83K3M (Lanosterol) 4964P6T9RB (Aldosterone) |
| تواريخ الأحداث: | Date Created: 20220509 Date Completed: 20220617 Latest Revision: 20220810 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.jsbmb.2022.106116 |
| PMID: | 35533918 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-1220 |
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| DOI: | 10.1016/j.jsbmb.2022.106116 |