» Articles » PMID: 36551196

The Similarities and Differences Between the Effects of Testosterone and DHEA on the Innate and Adaptive Immune Response

Overview
Journal Biomolecules
Publisher MDPI
Date 2022 Dec 23
PMID 36551196
Authors
Affiliations
Soon will be listed here.
Abstract

Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.

Citing Articles

Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy.

Yalcinkaya A, Yalcinkaya R, Sardh F, Landegren N Front Immunol. 2025; 15:1501364.

PMID: 39885993 PMC: 11779622. DOI: 10.3389/fimmu.2024.1501364.


Exploring How Adipose Tissue, Obesity, and Gender Influence the Immune Response to Vaccines: A Comprehensive Narrative Review.

De Sanctis J, Balda Noria G, Garcia A Int J Mol Sci. 2025; 26(2).

PMID: 39859575 PMC: 11765591. DOI: 10.3390/ijms26020862.


Exploring the role of sex hormones and gender diversity in multiple sclerosis.

Nesbitt C, van der Walt A, Butzkueven H, Cheung A, Jokubaitis V Nat Rev Neurol. 2024; 21(1):48-62.

PMID: 39658653 DOI: 10.1038/s41582-024-01042-x.


Dehydroepiandrosterone and Its Metabolite 5-Androstenediol: New Therapeutic Targets and Possibilities for Clinical Application.

Fedotcheva T, Uspenskaya M, Ulchenko D, Shimanovsky N Pharmaceuticals (Basel). 2024; 17(9).

PMID: 39338348 PMC: 11435263. DOI: 10.3390/ph17091186.


Correlation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with serum α-klotho levels in US middle-aged and older individuals: Results from NHANES 2007-2016.

Du R, Liu J, Tang X, Chen Z, Guan L, Gao W Prev Med Rep. 2024; 46:102877.

PMID: 39309699 PMC: 11415581. DOI: 10.1016/j.pmedr.2024.102877.


References
1.
Riggs D, Roberts P, Chirillo S, Cheung-Flynn J, Prapapanich V, Ratajczak T . The Hsp90-binding peptidylprolyl isomerase FKBP52 potentiates glucocorticoid signaling in vivo. EMBO J. 2003; 22(5):1158-67. PMC: 150341. DOI: 10.1093/emboj/cdg108. View

2.
Araneo B, Dowell T, Diegel M, Daynes R . Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells. Blood. 1991; 78(3):688-99. View

3.
Roden A, Moser M, Tri S, Mercader M, Kuntz S, Dong H . Augmentation of T cell levels and responses induced by androgen deprivation. J Immunol. 2004; 173(10):6098-108. DOI: 10.4049/jimmunol.173.10.6098. View

4.
Xie S, Chen M, Yan B, He X, Chen X, Li D . Identification of a role for the PI3K/AKT/mTOR signaling pathway in innate immune cells. PLoS One. 2014; 9(4):e94496. PMC: 3981814. DOI: 10.1371/journal.pone.0094496. View

5.
Massa M, David C, Jorg S, Berg J, Gisevius B, Hirschberg S . Testosterone Differentially Affects T Cells and Neurons in Murine and Human Models of Neuroinflammation and Neurodegeneration. Am J Pathol. 2017; 187(7):1613-1622. DOI: 10.1016/j.ajpath.2017.03.006. View