Reduced levels of oestrogen receptor β mRNA in Swedish patients with CFS, 2007, Grans et al

Reduced levels of oestrogen receptor β mRNA in Swedish patients with chronic fatigue syndrome
Hanna Gräns, Maria Nilsson, Karin Dahlman‐Wright, and Birgitta Evengård
J Clin Pathol. 2007 Feb; 60(2): 195–198. doi: 10.1136/jcp.2005.035956

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860629/

My Analysis

This is an older paper (2007) with a finding that doesn't seem to have been discussed on S4ME. ME/CFS patients were found to have reduced expression of oestrogen receptor β. I can't find many references to oestrogen receptors or oestrogen related receptors on the forum and it may be an avenue for further research. It may explain the gender split in ME/CFS and these receptors are known to be implicated in exercise.

I stumbled upon this paper after reading about an "exercise pill" that is proposed in this forthcoming American Chemical Society presentation. The presentation notes that "the metabolic changes associated with exercise kick off with the activation of specialized proteins, known as estrogen-related receptors (ERRs), which come in three forms: ERRα, ERRβ and ERRγ".

The team gave their mice a new compound that activated these ERRs and they increased their fatigue-resistant fibres. This seems relevant to the findings of Appelman et al that "observed a higher proportion of highly fatigable glycolytic fibers in the vastus lateralis muscle in long COVID patients".

I note that oestrogen related receptors and oestrogen receptors appear to be different things.

Abstract
Background
Chronic fatigue syndrome (CFS) is an illness with unknown aetiology and pathophysiology. The difference in incidence by sex observed for CFS indicates a role for oestrogen and oestrogen receptors in disease development. Furthermore, an immunomediated pathogenesis has been suggested for CFS, providing an additional connection to oestrogen, which displays immunomodular functions.

Aims
To investigate a possible association of oestrogen receptor (ER) mRNAs and two ERβ single‐nucleotide polymorphisms (SNPs) with CFS.

Methods
Messenger RNA levels of ERα, ERβ wt and ERβ cx were investigated in peripheral blood mononuclear cells from 30 patients with CFS and 36 healthy controls by quantitative real‐time polymerase chain reaction. Two ERβ SNPs were scored in the same material.

Results
The CFS group showed significantly lower mRNA expression levels of ERβ wt compared with the healthy control group. No differences were observed for ERα or ERβ cx between patients and controls. There were no significant differences in frequency for the investigated ERβ SNPs between cases and controls.

Conclusions
The reduced ERβ wt expression level observed in this study is consistent with an immune‐mediated pathogenesis of CFS. Additionally, the observation that ERβ wt expression is decreased in CFS could provide an entry point to identify interesting, potentially disease‐causing, candidate molecules for further study. A possible connection between oestrogen, oestrogen receptors and CFS should be evaluated further.