Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men
- Lund University, Sweden
- Warsaw University of Life Sciences, Poland
Abstract
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: a) before GnRH antagonist administration; b) 3 weeks later, just before testosterone undecanoate injection, and c) after additional 2 weeks. Subsequently they were analysed 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 cardio-metabolic parameters, bone mineral density as well as androgen receptor CAG repeat lengths, were explored.
Results:
Using ROC 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 levels 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 ReproUnion 2.0 (grant no 20201846), which is funded by the Interreg V EU program.
Data availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (60) partner repository with the dataset identifier PXD024448.Supplementary tables (datasets):https://doi.org/10.6084/m9.figshare.14875431Source data of the Figures can be found on:https://doi.org/10.6084/m9.figshare.14875431Supplementary Figure S1 (Figure 2-figure supplement 1):https://doi.org/10.6084/m9.figshare.14876562
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Supplementary tables, Novel protein markers of androgen activity in humans with potential clinical valuedoi.org/10.6084/m9.figshare.14875431.v2.
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Supplementary Figure S1, Novel protein markers of androgen activity in humans with potential clinical value.doi.org/10.6084/m9.figshare.14876562.v1.
Article and author information
Author details
Aleksander Giwercman
Krzysztof Pawlowski
Funding
ReproUnion (20201846)
- Aleksander Giwercman
Swedish Governmental Fund for Clinical Research
- Aleksander Giwercman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: All subjects were enrolled with informed written consent. The two studies from which they were recruited were approved by the Swedish Ethical Review Authority (Approval number: DNR 2014/311, date of approval 8 May 2014; DNR 2011/1, date of approval 11 January 2011).
Copyright
© 2022, Giwercman et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men
eLife 11:e74638.
https://doi.org/10.7554/eLife.74638
