Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone
| Autor: | Riaan Ehlers, Amanda C. Swart, Liezl M. Bloem, Antonio Serafin, Jonathan L. Quanson, Therina du Toit |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Glucuronidation urologic and male genital diseases Biochemistry Steroid 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Endocrinology Internal medicine LNCaP medicine Molecular Biology Androsterone Chemistry Cell Biology medicine.disease Androgen Androgen receptor 030104 developmental biology 030220 oncology & carcinogenesis Dihydrotestosterone Molecular Medicine medicine.drug |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 166:54-67 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/j.jsbmb.2016.06.009 |
| Popis: | Adrenal C19 steroids serve as precursors to active androgens in the prostate. Androstenedione (A4), 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT) are metabolised to potent androgen receptor (AR) agonists, dihydrotestosterone (DHT), 11-ketotestosterone (11KT) and 11-ketodihydrotestosterone (11KDHT). The identification of 11OHA4 metabolites, 11KT and 11KDHT, as active androgens has placed a new perspective on adrenal C11-oxy C19 steroids and their contribution to prostate cancer (PCa). We investigated adrenal androgen metabolism in normal epithelial prostate (PNT2) cells and in androgen-dependent prostate cancer (LNCaP) cells. We also analysed steroid profiles in PCa tissue and plasma, determining the presence of the C19 steroids and their derivatives using ultra-performance liquid chromatography (UHPLC)- and ultra-performance convergence chromatography tandem mass spectrometry (UPC2-MS/MS). In PNT2 cells, sixty percent A4 (60%) was primarily metabolised to 5α-androstanedione (5αDIONE) (40%), testosterone (T) (10%), and androsterone (AST) (10%). T (30%) was primarily metabolised to DHT (10%) while low levels of A4, 5αDIONE and 3αADIOL (≈20%) were detected. Conjugated steroids were not detected and downstream products were present at |
| Databáze: | OpenAIRE |
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