Monocyte–Macrophage System as a Target for Estrogen and Selective Estrogen Receptor Modulators

Abstract

Postmenopausal decline of estrogen production is associated with development of several degenerative disorders such as osteoporosis, neuroinflammatory diseases and vascular wall degeneration. These are associated with the activation of the cells of the monocyte-macrophage system in a context-dependent manner. Estrogen regulates differentiation, maturation and function of many cell types in this system directly or indirectly via other cells by autocrine/paracrine mechanisms. Estrogen effects on the monocyte-macrophage system are primarily repressive. Most of these effects are mediated by repression of expression of genes for cytokines or modulation of other inflammatory mediators by the estrogen receptor (ER)-dependent or nongenomic pathways. The ER-dependent mechanisms mostly involve modulation of the nuclear factor kappa B (NF-kappaB) pathway for transcriptional regulation of cytokine or other mediator genes. In the context of hormone-regulated cancer, estrogen can influence production of cytokines or other inflammatory mediators by both tumor cells and tumor-invading macrophages. The interactions of breast and prostate cancer cells with tumor-associated macrophages (TAMs) may play an important role in tumor progression and even in the development of resistance to hormonal treatment. Regulation of the monocyte-macrophage system by estrogen and cross-talk between the ER and cytokine-mediated pathways provides multiple novel targets for development of selective ER modulator (SERM) molecules for prevention and treatment of postmenopausal degenerative and neoplastic diseases.

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

“…Chez la souris, l'E2 en se liant au REβ réduit l'expression de COX-2 et la formation de la PGE2 et diminue l'inflammation microgliale (Baker et al, 2004 ;Vegeto et al, 2001). Dans des modèles de monocytes similaires à celui développé au sein de notre laboratoire, l'E2 exerce également des effets anti-inflammatoires via la liaison aux REs exprimés par ce type cellulaire en modulant la production de NFκB, de chimiokines (Harkonen et Vaananen, 2006 ;Janis et al, 2004) et en diminuant la production de PGE2 (Miyagi et al, 1993).…”

Roles and Mechanisms of Estrogen and Estrogen Receptors in Breast Cancer Resistant to Chemotherapy

“…Estrogen regulates differentiation, maturation and function of many cell types in monocytemacrophage system directly or indirectly via other cells by autocrine/paracrine mechanisms (73). Estrogen effects on this system are primarily repressive, and mainly mediated by repression of expression of genes for cytokines or modulation of other inflammatory mediators by the ER-dependent or nongenomic pathways.…”

“…The ER-dependent mechanisms mostly involve modulation of the NF-kappaB pathway for transcriptional regulation of cytokine or other mediator genes. In the context of hormone-regulated cancer, estrogen can influence production of cytokines or other inflammatory mediators by both tumor cells and tumor-invading macrophages (73). The interactions of breast cancer cells with tumor-associated macrophages, regulation of the monocyte-macrophage system by estrogen and cross-talk between the ER and cytokine-mediated pathways, may play an important role in tumor progression as well as the development of resistance to anticancer treatment (73)(74)(75).…”

Evaluation Of Salivary IL-1Beta And IL-6 Levels In Pregnant And Postpartum Women

“…The study design included the following groups: 1) pregnant women (n=96) who were in their second trimester (weeks [16][17][18][19][20][21][22][23][24] or third trimester (weeks 25-34), 2) postpartum women (n=96) who were evaluated 6 months after delivery.…”

“…19,20 Sex-steroid hormones at physiological concentrations had an inhibitory effect on the secretion of pro-inflammatory cytokines, including IL-1β and IL-6.…”