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

Giwercman, Aleksander LU ; Sahlin, K. Barbara ; Pla Parada, Indira LU orcid ; Pawlowski, Krzysztof LU ; Fehninger, Carl ; Lundberg Giwercman, Yvonne LU ; Leijonhufvud, Irene LU ; Appelqvist, Roger LU ; Marko-Varga, György LU and Sanchez, Aniel LU , et al. (2022) In eLife 11.
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: (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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
androgens, biomarker, human, hypogonadism, medicine
in
eLife
volume
11
publisher
eLife Sciences Publications
external identifiers
  • scopus:85128487338
  • pmid:35230239
ISSN
2050-084X
DOI
10.7554/eLife.74638
language
English
LU publication?
yes
id
5296ef02-fb6a-4d54-a16e-4197c94fe8c6
date added to LUP
2022-07-05 14:52:22
date last changed
2024-06-11 18:55:42
@article{5296ef02-fb6a-4d54-a16e-4197c94fe8c6,
  abstract     = {{<p>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 (&lt;8 nmol/l) vs normal (&gt;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.</p>}},
  author       = {{Giwercman, Aleksander and Sahlin, K. Barbara and Pla Parada, Indira and Pawlowski, Krzysztof and Fehninger, Carl and Lundberg Giwercman, Yvonne and Leijonhufvud, Irene and Appelqvist, Roger and Marko-Varga, György and Sanchez, Aniel and Malm, Johan}},
  issn         = {{2050-084X}},
  keywords     = {{androgens; biomarker; human; hypogonadism; medicine}},
  language     = {{eng}},
  month        = {{03}},
  publisher    = {{eLife Sciences Publications}},
  series       = {{eLife}},
  title        = {{Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men}},
  url          = {{http://dx.doi.org/10.7554/eLife.74638}},
  doi          = {{10.7554/eLife.74638}},
  volume       = {{11}},
  year         = {{2022}},
}