Regulatory Roles of Estrogens in Psoriasis

Abstract

Psoriasis is a common chronic inflammatory skin disease of the interleukin (IL)-23/IL-17 axis. The severity of psoriasis has been reported as higher in men than in women. The immunoregulatory role of female sex hormones has been proposed to be one of the factors responsible for sex differences. Among female sex hormones, estrogens have been suggested to be significantly involved in the development of psoriasis by various epidemiological and in vitro studies. For example, the severity of psoriasis is inversely correlated with serum estrogen levels. In vitro, estrogens suppress the production of psoriasis-related cytokines such as IL-1β and IL-23 from neutrophils and dendritic cells, respectively. Furthermore, a recent study using a mouse psoriasis model indicated the inhibitory role of estrogens in psoriatic dermatitis by suppressing IL-1β production from neutrophils and macrophages. Understanding the role and molecular mechanisms of female sex hormones in psoriasis may lead to better control of the disease.

Keywords: estrogen; female sex hormone; progesterone; psoriasis.

Figure 1

A scheme of estrogen receptors and the intracellular signaling pathway. In genomic pathway, 17β-estradiol (E2) binds to estrogen receptor α and estrogen receptor β in the cytoplasm. It forms dimer and translocates to the nucleus. Then, they bind to estrogen receptor element (ERE) and activate the transcription of downstream genes (classical genomic pathway). Or, they interact with other transcription factor (TF)s, such as NF-κB, specificity protein 1 (SP1), activator protein-1 (AP-1), and CCAAT/enhancer binding protein β (C/EBPβ), and prevent their binding to the transcription factor regulatory element (TFRE) (non-classical genomic pathway), leading to the regulation of their target gene expression. In non-genomic pathway, E2 binds to G protein-coupled estrogen receptor 1 (GPER1) and it regulates mitogen-activated protein kinase (MAPK), calcium (Ca) release, and cyclic adenosine monophosphate (cAMP). Created with Biorender.com.

Figure 2

A scheme of possible functions and the mechanisms of estrogen in psoriatic inflammation. E2 play anti-psoriatic functions by downregulating IL-1β production from neutrophils (Neus) and monocytes/macrophages (Macs) through ERα and ERβ. However, in a certain condition, E2 may play facilitating role on psoriatic inflammation by inducing IL-23 production from dendritic cells (DCs) through ERα. Solid lines show the findings from in vivo studies and dotted lines show the findings from in vitro or other disease model studies. Created with Biorender.com.