Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men.

Autor:	Giwercman A; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmo, Sweden., Sahlin KB; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden., Pla Parada I; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden., Pawlowski K; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Department of Experimental Design and Bioinformatics, Faculty of Agriculture and Biology, Warsaw University of Life Sciences SGGW, Warszawa, Poland.; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States., Fehninger C; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden., Lundberg Giwercman Y; Molecular Genetic Reproductive Medicine, Department of Translational Medicine, Lund University, Lund, Sweden., Leijonhufvud I; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Malmo, Sweden., Appelqvist R; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden., Marko-Varga G; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden.; First Department of Surgery, Tokyo Medical University, Nishishinjiku Shinjiku-ku, Japan., Sanchez A; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden., Malm J; Section for Clinical Chemistry, Department of Translational Medicine, Lund University, Skåne University Hospital Malmö, Lund, Sweden.; Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund, Sweden.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Mar 01; Vol. 11. Date of Electronic Publication: 2022 Mar 01.
DOI:	10.7554/eLife.74638
Abstrakt:	Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program. Competing Interests: AG received consulting fees from Besins Healthcare. The author has no other competing interests to declare, KS, IP, KP, CF, YL, IL, RA, GM, AS, JM No competing interests declared (© 2022, Giwercman et al.)
Databáze:	MEDLINE
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