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.

Keywords: estrogen; infection; inflammation; sex hormones.

Figure 1

A summary of the sources of estrogen production in the body (left) and schematic diagram of both “classical” and “nongenomic” estrogen signaling pathways (right). Abbreviations: ATP: adenosine 5’-triphosphate, cAMP: cyclic adenosine monophosphate, ER: estrogen receptor, ERE: estrogen-responsive element, TF: transcription factor, α_s: alpha subunit, β/γ: beta/gamma subunit, MAPK: mitogen-activated protein kinase, PI3K: phosphoinositide 3-kinase, PLC: phosphoinositide-specific phospholipase C, and IP3: inositol triphosphate. Created with Biorender.com, accessed on 9 December 2021.

Figure 2

Examples of reasons estrogen levels vary and change. Females experience fluctuating estrogen levels during menstruation, in addition to dramatic changes in hormone levels during pregnancy and following menopause. Exogenous estrogens from dietary or therapeutic (hormonal contraceptives, HRT) sources also alter estrogenic effects in the body. Created with Biorender.com, accessed on 15 January 2022.