ArticleImmunity & ageing : I & A2016
Role of androgens in dhea-induced rack1 expression and cytokine modulation in monocytes.
Article in Immunity & ageing : I & A, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study.Respiratory research · 2018Trial
- Endocrine Disrupting Toxicity of Bisphenol A and Its Analogs: Implications in the Neuro-Immune Milieu.Journal of xenobiotics · 2025Review
- The roles of RACK1 in the pathogenesis of Alzheimer's disease.Journal of biomedical research · 2024Article
- Low testosterone predicts hypoxemic respiratory insufficiency and mortality in patients with COVID-19 disease: another piece in the COVID puzzle.Journal of endocrinological investigation · 2022Article
- Sex steroid modulation of macrophages within the prostate tumor microenvironment.American journal of clinical and experimental urology · 2022Article
- Rosmarinic acid ameliorates acetaminophen-induced acute liver injury in mice via RACK1/TNF-α mediated antioxidant effect.Pharmaceutical biology · 2021Article
- Article
- Neuroendocrine Modulation of the Immune Response after Trauma and Sepsis: Does It Influence Outcome?Journal of clinical medicine · 2020Review
- TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands.Genes to cells : devoted to molecular & cellular mechanisms · 2020Article
- Article
- Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung.Frontiers in immunology · 2020Review
- Dehydroepiandrosterone: a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient.Burns & trauma · 2019Review
- Do Androgens Modulate the Pathophysiological Pathways of Inflammation? Appraising the Contemporary Evidence.Journal of clinical medicine · 2018Review
- Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence.International journal of molecular sciences · 2017Review
- Interaction of the Mineralocorticoid Receptor With RACK1 and Its Role in Aldosterone Signaling.Endocrinology · 2017Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOver the past fifteen years, we have demonstrated that cortisol and dehydroepiandrosterone (DHEA) have opposite effects on the regulation of protein kinase C (PKC) activity in the context of the immune system. The anti-glucocorticoid effect of DHEA is also related to the regulation of splicing of the glucocorticoid receptor (GR), promoting the expression of GRβ isoform, which acts as a negative dominant form on GRα activity. Moreover, it is very well known that DHEA can be metabolized to androgens like testosterone, dihydrotestosterone (DHT), and its metabolites 3α-diol and 3β-diol, which exert their function through the binding of the androgen receptor (AR). Based on this knowledge, and on early observation that castrated animals show results similar to those observed in old animals, the purpose of this study is to investigate the role of androgens and the androgen receptor (AR) in DHEA-induced expression of the PKC signaling molecule RACK1 (Receptor for Activated C Kinase 1) and cytokine production in monocytes.
resultsHere we demonstrated the ability of the anti-androgen molecule, flutamide, to counteract the stimulatory effects of DHEA on RACK1 and GRβ expression, and cytokine production. In both THP-1 cells and human peripheral blood mononuclear cells (PBMC), flutamide blocked the effects of DHEA, suggesting a role of the AR in these effects. As DHEA is not considered a direct AR agonist, we investigated the metabolism of DHEA in THP-1 cells. We evaluated the ability of testosterone, DHT, and androstenedione to induce RACK1 expression and cytokine production. In analogy to DHEA, an increase in RACK1 expression and in LPS-induced IL-8 and TNF-α production was observed after treatment with these selected androgens. Finally, the silencing of AR with siRNA completely prevented DHEA-induced RACK1 mRNA expression, supporting the idea that AR is involved in DHEA effects.
conclusionsWe demonstrated that the conversion of DHEA to active androgens, which act via AR, is a key mechanism in the effect of DHEA on RACK1 expression and monocyte activation. This data supports the existence of a complex hormonal balance in the control of immune modulation, which can be further studied in the context of immunosenescence and endocrinosenescence.
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