Estrogen and Signaling in the Cells of Immune System

Abstract

Hypothalamus-pituitary-gonadal axis regulation of estrogen, which acts on reproductive tissues, is well established. However, it is also evident that estrogens physiologically act on not only reproductive tissues but also on a broad range of tissues such as immune system. It is well documented that estrogen regulates all facets of the immunoregulation thereby affecting the outcome of autoimmune and inflammatory immune responses. Given the broader role of estrogen in immunobiology, it is important to understand how estrogens act on the cells of the immune system. Estrogens act in estrogen receptor dependent and/or independent manner to affect the regulation of cytokines and chemokines. This review focuses on sources and biosynthesis of estrogens, differential expression of estrogen receptors on the cells of immune system, key signaling pathways and its effect on the induction of key pro-and anti-inflammatory cytokines. Since estrogen has contrasting effects in female-predominant autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE), we briefly overview the mechanistic role of estrogen on these chronic diseases. Recent evidence suggests that estrogens also alter microRNAs, which regulate a broad range of transcription of genes. The review also addresses this and other newly discovered mechanisms of estrogen-induced immunomodulation in health and disease.

The Immune System Is a Natural Target for Estrogen Action: Opposing Effects of Estrogen in Two Prototypical Autoimmune Diseases

“…These include: genetics; epigenetics (miRNA, methylation, and histone deacetylation); infections; and external and internal environmental triggers including hormones and microbiome. A majority of autoimmune diseases occur predominantly in women, a feature also noted in many animal models of autoimmune diseases ( 5 , 69 ). Initially, it was presumed that the sex bias is related to differences in sex steroids, but it is now evident that several other factors contribute to the sex bias of autoimmune diseases that include X chromosomal abnormalities, X-chromosomal inactivation, and fetal microchimerism.…”

“…There is now an enormous amount of literature on estrogen’s effects on the cells of the innate immune system [neutrophils, macrophages/monocytes, natural killer cells, dendritic cells (DC)], and the adaptive immune system (T and B cells). These aspects have been comprehensively covered in many reviews ( 5 – 7 ) and hence are beyond the scope of this minireview. Estrogens have been shown to regulate neutrophil numbers and functions that include chemotaxis, infiltration, production of superoxide anion and myeloperoxidase, induction of chemokines (cytokine induced neutrophil chemoattractants such as CINC-1, CINC-2β, and CINC-3, monocyte chemoattractant protein-1), and cytokines (e.g., TNF-α, IL-6, IL-1β) ( 8 – 10 ).…”

“…Although the principal function of sex steroid action is to regulate reproductive functions, studies in diverse fields have unequivocally established that sex steroids also act on diverse non-reproductive tissues include immune, central nervous, cardiovascular, and skeletal systems, as well as cells from liver, skin, and kidneys ( 1 – 5 ). In this brief review, we will discuss estrogen effects on the immune cells, the estrogen-specific receptor expression on cells of the immune system, and key estrogen-receptor mediated-signaling pathways involved.…”

Sex ratio among childhood cancers by single year of age

“…Hormones may also indirectly impact the development of leukemias and lymphomas. In adults, estrogen may increase the immune response 45,46 while increasing testosterone may dampen the immune response, 47 although these findings warrant validation in pediatric populations.…”

Efek Pemberian Ekstrak Tepung Kedelai Hitam (Glycine soja) Terhadap Leukosit Mencit (Mus musculusL.) Implantasi Pasca Ovariektomi

“…Hal ini diduga bahwa pada kontrol positif, terdapat senyawa estradiol yang merupakan salah satu bentuk dari struktur estrogen yang paling utama serta dominan dalam tahap dimulainya reproduksi hingga fase penuaan. Selain itu, bentuk hormon estrogen ini memiliki afinitas kuat sehingga sangat mudah disintesis dalam tubuh selama perkembangan reproduksi (Khan et al, 2012). Jumlah leukosit pada perlakuan (P1: 6350,00 c ± 868,188; P2: 6525,00 c ± 470,815) juga lebih tinggi dibandingkan dengan kontrol negatif.…”