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
Further reading
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- Medicine
- Neuroscience
It has been well documented that cold is an enhancer of lipid metabolism in peripheral tissues, yet its effect on central nervous system lipid dynamics is underexplored. It is well recognized that cold acclimations enhance adipocyte functions, including white adipose tissue lipid lipolysis and beiging, and brown adipose tissue thermogenesis in mammals. However, it remains unclear whether and how lipid metabolism in the brain is also under the control of ambient temperature. Here, we show that cold exposure predominantly increases the expressions of the lipid lipolysis genes and proteins within the paraventricular nucleus of the hypothalamus (PVH) in male mice. Mechanistically, by using innovatively combined brain-region selective pharmacology and in vivo time-lapse photometry monitoring of lipid metabolism, we find that cold activates cells within the PVH and pharmacological inactivation of cells blunts cold-induced effects on lipid peroxidation, accumulation of lipid droplets, and lipid lipolysis in the PVH. Together, these findings suggest that PVH lipid metabolism is cold sensitive and integral to cold-induced broader regulatory responses.
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- Medicine
Background:
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a severe and deadly adverse event following ERCP. The ideal method for predicting PEP risk before ERCP has yet to be identified. We aimed to establish a simple PEP risk score model (SuPER model: Support for PEP Reduction) that can be applied before ERCP.
Methods:
This multicenter study enrolled 2074 patients who underwent ERCP. Among them, 1037 patients each were randomly assigned to the development and validation cohorts. In the development cohort, the risk score model for predicting PEP was established via logistic regression analysis. In the validation cohort, the performance of the model was assessed.
Results:
In the development cohort, five PEP risk factors that could be identified before ERCP were extracted and assigned weights according to their respective regression coefficients: –2 points for pancreatic calcification, 1 point for female sex, and 2 points for intraductal papillary mucinous neoplasm, a native papilla of Vater, or the pancreatic duct procedures (treated as ‘planned pancreatic duct procedures’ for calculating the score before ERCP). The PEP occurrence rate was 0% among low-risk patients (≤0 points), 5.5% among moderate-risk patients (1–3 points), and 20.2% among high-risk patients (4–7 points). In the validation cohort, the C statistic of the risk score model was 0.71 (95% CI 0.64–0.78), which was considered acceptable. The PEP risk classification (low, moderate, and high) was a significant predictive factor for PEP that was independent of intraprocedural PEP risk factors (precut sphincterotomy and inadvertent pancreatic duct cannulation) (OR 4.2, 95% CI 2.8–6.3; p<0.01).
Conclusions:
The PEP risk score allows an estimation of the risk of PEP prior to ERCP, regardless of whether the patient has undergone pancreatic duct procedures. This simple risk model, consisting of only five items, may aid in predicting and explaining the risk of PEP before ERCP and in preventing PEP by allowing selection of the appropriate expert endoscopist and useful PEP prophylaxes.
Funding:
No external funding was received for this work.
