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

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.

Sex differences in colorectal cancer: with a focus on sex hormone–gut microbiome axis

“…It also prolongs B-cell survival, creating an inflammatory microenvironment with altered intestinal permeability, which leads to the migration of gut microbiota into the lamina propria, promoting inflammation [9]. Androgens are generally considered immunosuppressive, but some studies have found that testosterone and DHEA promote the activation of regulatory T cells, thereby suppressing Th17-type responses [114]. Others have demonstrated that testosterone inhibits T-cell proliferation, modulates macrophage function, and promotes inflammatory responses [115].…”

Patient Subtyping Analysis of Baseline Multi-omic Data Reveals Distinct Pre-immune States Predictive of Vaccination Responses

“…Up-regulated N1-acetylspermidine was previously associated with favorable outcome in severe COVID-19 patients and shown to have anti-inflammatory and immunostimulatory effects [50]. Dehydroepiandrosterone (DHEA, 5-Androsten-3beta-17-one) has been known to regulate immune function and was among the top down-regulated metabolites in the S-HiAI subtype [52]. Mangiferin, a natural flavonoid compound with anti-inflammatory and anti-oxidant properties, and Evodiamine, a supplement with anti-tumor and anti-inflammatory pharmacological effects, were both up-regulated in the S-LoAI/HiII (low adaptive/high innate immunity) subtype.…”

Influence of androgens on the innate immune system

“…61 Upon treating healthy men with a GnRH antagonist, simulating medical castration, there was an increase in the percentage of NK cells. 62 In a study by…”

“…Natural killer (NK) cells also make up the first line of defense due to their direct cytotoxic activity on infected cells 61 . Upon treating healthy men with a GnRH antagonist, simulating medical castration, there was an increase in the percentage of NK cells 62 . In a study by Solerte et al., dehydroepiandrosterone increased the cytotoxic activity of NK cells on tumor cells in vitro through the increasing synthesis and secretion of insulin‐like growth factor‐I, thereby positively modulating immunity 63 …”