The Impact of Estrogens and Their Receptors on Immunity and Inflammation during Infection

Abstract

Sex hormones, such as estrogen and testosterone, are steroid compounds with well-characterized effects on the coordination and development of vertebrate reproductive systems. Since their discovery, however, it has become clear that these “sex hormones” also regulate/influence a broad range of biological functions. In this review, we will summarize some current findings on how estrogens interact with and regulate inflammation and immunity. Specifically, we will focus on describing the mechanisms by which estrogens alter immune pathway activation, the impact of these changes during infection and the development of long-term immunity, and how different types of estrogens and their respective concentrations mediate these outcomes.

Estrogen Acts Through Estrogen Receptor-β to Promote Mannan-Induced Psoriasis-Like Skin Inflammation

“…Interestingly, both ER-α and GPR30 are commonly associated with anti-inflammatory phenotypes, while ER-β, was shown to be associated with proinflammatory functions as well as an anti-inflammatory role. The differences in the effect of estrogen on cells could possibly be due to variations in receptor expression in cell types and prevailing different physiological states ( 56 ). However, the mechanisms behind sex differences in the expression of ERs in immune cells are not clear.…”

Epigenetic regulation and T-cell responses in endometriosis – something other than autoimmunity

“…It is therefore logical that, unlike in autoimmune disorders where targeted immunosuppression is a priority, the treatment in endometriosis concerns hormonal imbalances and is primarily aimed at decreasing the endogenous ovarian production of estrogens (190,191). In general, it is now appreciated that estrogens, and in particular E2, can control proinflammatory signals/pathways (192). The antiinflammatory effects of estrogens are associated mostly with signaling via ERa and GPER, whereas even if not without controversy, an increased ratio of ERb is associated with proinflammatory signatures (193)(194)(195).…”

“…The antiinflammatory effects of estrogens are associated mostly with signaling via ERa and GPER, whereas even if not without controversy, an increased ratio of ERb is associated with proinflammatory signatures (193)(194)(195). Variations in the expression of different estrogen receptor types may lead to some discrepancies in understanding the effects of estrogen on the immune system in health and endometriosis (192,196). Markedly higher levels of ERb and lower levels of ERa in human endometriotic stromal cells corresponds to EnSCs compared with EnSCs within eutopic endometrial tissues were reported (197,198).…”

Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis

“…Accordingly, the promoters of a large number of sex-biased genes harboring hormone-response elements (HREs) are recognized by transcription factors (TFs) such as the estrogen receptor-α (ERα), glucocorticoid receptor (GR), as well as two X-linked TFs the androgen receptor (AR) and ELK1 [40]. Androgen-response elements (AREs) and estrogen-response elements (EREs) are present in the promoters of several innate immunity genes [41].…”

“…In addition to the AR, testosterone also cross-binds with the progesterone and ERs, although with a lower affinity, whereas DHT binds more specifically to the AR. Genes encoding many immunostimulatory proteins (e.g., IFN-γ, TLR7) have hormone-response elements (HREs) in their promoters, which allow bound sex hormone receptors with nuclear localization sequences to act as transcription factors (TFs), leading to altered gene expression [41]. In human studies, estrogen has been deemed to have an immunoenhancing effect on the immune system, whereas testosterone and progesterone are considered to be immunosuppressive [146].…”